CN1465704A - Cancer suppressor gene PINX1 and use thereof - Google Patents

Abstract

The present invention discloses a method for diagnosing carcinosis of pith mother cell tumor, it includes the detection of individual PINX1 gene, transcript and/or protein, and said invention also discloses its correspondent detection kit and its medicine composition for curing carcinosis, specially for curing mother cell tumor and its curing method.

Description

Cancer suppressor gene PINX 1 and application thereof

Technical field

The present invention relates to biotechnology and medical field.More specifically, the present invention relates to utilize method for cancer such as diagnosis of cancer suppressor gene PINX 1 gene and coded product thereof and treatment medulloblastoma, and contain PINX1 gene and/or proteic pharmaceutical composition.

Background technology

The modal malignant tumour of encephalic Childhood that medulloblastoma being, sickness rate accounts for 1/5th of brain tumor sum.Not only grade malignancy is high and have infringement for it, spinal cord easily takes place shift, and patient's long-term surviving rate is low, is the important diseases of serious human survival.

The defective that the overexpression of cellular proto-oncogene, the inactivation of cancer suppressor gene and dna mismatch are repaired gene is the major reason that various tumours, cancer take place and develop.Different is, numerous studies show that activation, the amplification of proto-oncogene and cross be expressed in the medulloblastoma uncommonly, be the cancer suppressor gene inactivation of feature but show as with allele heterozygosity disappearance (LOH) more.

Yet, up to now, still do not disclose the definite reason that medulloblastoma produces and develops, do not disclose medulloblastoma yet and have direct dependency with certain cancer suppressor gene and proteins encoded thereof.In addition, this area also lacks the effective means of the effective ways and the treatment medulloblastoma except that operation and radiotherapy of early diagnosis medulloblastoma.

PINX1 is called PIN2 interaction protein 1 again, and it is a kind of known protein, and essential information is as follows:

English: Homo sapiens PIN2-interacting protein 1 PINX1 (hepatocellular carcinoma-

related?putative?tumor?suppressor)

NCBI：Contig：NT_008010

mRNA：Homo?sapiens?PIN2-interacting?protein?1(PINX1)，mRNA

gi|16975485|ref|NM_017884.1|[6975485]

The dna sequence dna of PINX1 is shown in SEQ ID NO:1, and ORF is positioned at the 90-1073 position, 328 amino acid whose protein of the total length of encoding (SEQ ID NO:2).Other information of PINX1 can be from Http: //www.ncbi.nlm.nih.gov obtains.

Once there are some researches show that No. 8 the short arm of a chromosome were hot spot regions that the heterozygosity disappearance takes place in many cancers and the tumor tissues, strong prompting exists the cancer suppressor gene that plays a significant role herein in all kinds of tumours and cancer.Report simultaneously, be positioned the 8P23 zone PIN2 protein interactive protein 1 (PINX1) may with cell Telomerase vigor and apoptosis-related.But it is very few that people also understand for the function of PINX1, do not know the dependency of cancers such as itself and medulloblastoma.

Therefore, this area presses for the effective ways of new diagnosis of exploitation and treatment medulloblastoma, and relevant medicine, diagnostic techniques and reagent.

Summary of the invention

One object of the present invention just provides method for cancer and detection kit such as a kind of new diagnosis (especially early diagnosis) medulloblastoma.

Another object of the present invention provides a kind of method of new treatment cancer, especially medulloblastoma.

A further object of the present invention provides a kind of pharmaceutical composition of treatment cancer, especially medulloblastoma.

In a first aspect of the present invention, a kind of cancer to individuality is provided, the method diagnosed of medulloblastoma susceptibility especially, it comprises step:

Detect this individual PINX1 gene, transcript and/or albumen, and compare with normal PINX1 gene, transcript and/or albumen,

There are differences and just show this individuality cancer stricken, the possibility of especially suffering from medulloblastoma is higher than normal population.

Preferably, detected is gene or the transcript of PINX1, and with normal PINX1 nucleotide sequence comparing difference.More preferably, described difference is selected from: the 162nd G162 becomes A162 among the SEQ ID NO:1; The 367th C367 becomes T367 among the SEQ ID NO:1.

In a second aspect of the present invention, a kind of method of treatment cancer, especially medulloblastoma is provided, it comprises step: the normal PINX1 albumen of using safe and effective amount to the patient of the described treatment of needs.Preferably, PINX1 albumen is locally applied to tumor tissues.

In a third aspect of the present invention, provide a kind of PINX1 albumen aspect pharmaceutical compositions purposes and corresponding pharmaceutical compositions, it contains the people PINX1 albumen and the pharmaceutically acceptable carrier of safe and effective amount.Preferably, it is a targeted drug.

In a fourth aspect of the present invention, a kind of test kit of detection cancer, especially medulloblastoma is provided, it comprises the primer of specific amplification PINX1 gene or transcript.Preferably, it also contains and mutable site bonded probe.

In a fifth aspect of the present invention, a kind of method of single nucleotide polymorphism of the people of detection PINX1 gene is provided, it comprises step: (a) determine the 162nd and 367 Nucleotide in sequence shown in the SEQ ID of the people PINX1 gene NO:1; (b) whether detection exists single nucleotide polymorphism G 162 → A162 and the C367 → T367 that is selected from following group in described position.

Others of the present invention are because disclosing of the technology of this paper is conspicuous to those skilled in the art.

Description of drawings

Fig. 1 has shown the sequence variation in the PINX1 gene, and wherein the 162nd G162 becomes A162; The 367th C367 becomes T367.

Embodiment

The inventor is through extensive and deep research, find first and proved that PIN2 interaction protein 1 (PINX1) is a cancer suppressor gene, closely related with cancers such as medulloblastomas, its change will promote the generation and the development of medulloblastoma and other cancer, be one of immediate cause that causes cancer.Finished the present invention on this basis.

By 32 routine medulloblastoma samples and part being contrasted the research of blood sample, found many cases somatocyte PINX sudden change.Studies show that further people PINX1 and medulloblastoma are closely related, its normal expression is to suppress cancer particularly medulloblastoma generation and development, keeps the key of normal physiological state.According to albumen homology relatively, human PIN2 interaction protein 1 (PINX1) has higher conservative property between species, act on important.Simultaneously, expression study shows that the PINX1 gene is expressed in the many vital tissues of human body.Therefore the sudden change of human PIN2 interaction protein 1 (PINX1) is to cause the particularly major reason of medulloblastoma of human cancer, according to the medicine and the diagnoses and treatment technology of this gene and expression product thereof design, can be used for diagnosis and treat cancer such as human medulloblastoma.

In view of the variation of human PINX1 is one of immediate cause that causes medulloblastoma.Therefore, medicine and diagnoses and treatment technology according to this gene and expression product design thereof can be used for diagnosing and treating human cancer, especially medulloblastoma.

People PINX1 Nucleotide full length sequence of the present invention or its fragment can obtain with the method for pcr amplification method, recombination method or synthetic usually.For the pcr amplification method, can be according to the relevant nucleotide sequence of PINX1, especially open reading frame sequence designs primer, and with commercially available cDNA storehouse or by the prepared cDNA storehouse of ordinary method well known by persons skilled in the art as template, amplification and must relevant sequence.

In case obtained relevant sequence, just can obtain relevant sequence in large quantity with recombination method.This normally is cloned into carrier with it, changes cell again over to, separates obtaining relevant sequence then from the host cell after the propagation by ordinary method.

In addition, also the method for available synthetic is synthesized relevant sequence, especially fragment length more in short-term.Usually, by first synthetic a plurality of small segments, and then connect and to obtain the very long fragment of sequence.

The PINX1 encoding sequence is inserted suitable expression vector, change host cell again over to, just can isolate PINX1 albumen.

Based on new discovery of the present invention, PINX1 albumen or polypeptide have many-sided new purposes.These purposes include, but is not limited to: directly as pharmacological agent PINX1 protein function the disease due to the low or forfeiture (as various tumours, especially medulloblastoma), screen the material that promotes the PINX1 protein function with being used to, as antibody, polypeptide or other part.The peptide molecule that can stimulate people PINX1 protein function that can be used for seeking therapeutic value with the recombinant human PINX1 protein screening peptide library of expressing.

On the other hand, the present invention also comprises people PINX1 DNA or the polypeptide of its fragment coding has specific polyclonal antibody and monoclonal antibody, especially monoclonal antibody.Here, " specificity " is meant that antibody capable is incorporated into people PINX1 gene product or fragment.Preferably, refer to that those can combine with people PINX1 gene product or fragment but nonrecognition and be incorporated into the antibody of other irrelevant antigen molecule.Among the present invention antibody comprise those can in conjunction with and suppress the proteic molecule of people PINX1, comprise that also those do not influence the antibody of people PINX1 protein function.

The present invention not only comprises complete mono-clonal or polyclonal antibody, but also comprises having immunocompetent antibody fragment, as Fab ' or (Fab) 2 fragments; Heavy chain of antibody; Light chain of antibody; Genetically engineered strand Fv molecule; Or chimeric antibody.

Antibody of the present invention can be prepared by the known various technology of those skilled in that art.For example, the people PINX1 gene product of purifying or its have antigenic fragment, can be applied to animal to induce the generation of polyclonal antibody.Similarly, expressing human PINX1 albumen or its have antigenic segmental cell and can be used to immune animal and produce antibody.Multiple adjuvant can be used for the enhancing immunity reaction, includes but not limited to freund's adjuvant etc.

Antibody of the present invention also can be monoclonal antibody.This type of monoclonal antibody can utilize hybridoma technology to prepare.Antibody of the present invention comprises the antibody that can block people PINX1 protein function and the antibody that does not influence people PINX1 protein function.Each antibody-like of the present invention can utilize the fragment or the functional zone of people PINX1 gene product, obtains by the routine immunization technology.These fragments or functional zone can utilize recombinant methods or utilize Peptide synthesizer synthetic.Can come immune animal and produce with the gene product of producing in the prokaryotic cell prokaryocyte (for example E.Coli) with the unmodified form bonded antibody of people PINX1 gene product; With posttranslational modification form bonded antibody (as the albumen or the polypeptide of glycosylation or phosphorylation), can come immune animal and obtain with the gene product that produces in the eukaryotic cell (for example yeast or insect cell).

The proteic antibody of anti-people PINX1 can be used in the immunohistochemistry technology, detects the people PINX1 albumen in the biopsy specimen.A kind of preferred anti-PINX1 antibody is the antibody of the normal PINX1 of nonrecognition PINX1 (as SEQ ID NO:4) but identification suddenlys change, perhaps discerns normal PINX1 but the antibody of nonrecognition sudden change PINX1.Utilize this antibody to the proteic specificity difference of normal and unusual PINX1, the medulloblastoma susceptibility that can carry out protein level easily detects.

Utilize PINX1 albumen of the present invention,, can filter out with PINX1 albumen interactional material takes place, as inhibitor, agonist or antagonist etc. by various conventional screening methods.

PINX1 albumen of the present invention can used (administration) to the patient.Usually, can these materials are formulated in nontoxic, inert and the pharmaceutically acceptable aqueous carrier medium, wherein pH is about 5-8 usually, and preferably pH is about 6-8, although the pH value can be with being changed to some extent by preparation Substance Properties and illness to be treated.The pharmaceutical composition for preparing can carry out administration by conventional route, comprising (but being not limited to): intramuscular, intravenously, subcutaneous or topical (comprising administration in the knurl).Be preferably topical, for example administration in the knurl.

Normal PINX1 polypeptide can be directly used in disease treatment, for example, is used for the treatment of medulloblastoma aspect.When using PINX1 albumen of the present invention, also can use the medicament of other treatment tumour simultaneously.

The present invention also provides a kind of pharmaceutical composition, and it contains PINX1 albumen of the present invention and the pharmaceutically acceptable carrier or the vehicle of safe and effective amount.This class carrier comprises (but being not limited to): salt solution, damping fluid, glucose, water, glycerine, ethanol and combination thereof.Pharmaceutical preparation should be complementary with administering mode.Pharmaceutical composition of the present invention can be made into the injection form, for example is prepared by ordinary method with the physiological saline or the aqueous solution that contains glucose and other assistant agents.Pharmaceutical composition such as injection, tablet and capsule can be prepared by ordinary method.Pharmaceutical composition such as injection, solution, tablet and capsule should be made under aseptic condition.The dosage of activeconstituents is the treatment significant quantity, for example every day about 0.1 microgram/kg body weight-Yue 10 mg/kg body weight.In addition, polypeptide of the present invention also can use with the other treatment agent.

When making pharmaceutical composition, be that the PINX1 albumen of safe and effective amount or its antagonist, agonist are applied to Mammals, wherein this safe and effective amount is usually at least about 0.1 microgram/kg body weight, and in most of the cases be no more than about 10 mg/kg body weight, preferably this dosage is about 0.1 microgram/kg body weight-Yue 100 micrograms/kg body weight.Certainly, concrete dosage also should be considered factors such as route of administration, patient health situation, and these all are within the skilled practitioners skill.

The proteic polynucleotide of people PINX1 also can be used for multiple therapeutic purpose.Gene therapy technology can be used for treating because the cell proliferation due to the proteic expression of PINX1 of the proteic nothing expression of PINX1 or unusual/non-activity is unusual.The method that structure carries the recombinant viral vector of PINX1 gene be found in existing document (Sambrook, etal.).Recombinant human PINX1 gene can be packaged in the liposome in addition, and then is transferred in the cell.

Polynucleotide imports tissue or intracellular method comprises: polynucleotide directly is injected in the in-vivo tissue (as tumor tissues); Or external by carrier (as virus, phage or plasmid etc.) earlier with the polynucleotide transfered cell in, again cell is transplanted in the body etc.

The invention still further relates to the diagnostic testing process of quantitative and detection and localization people PINX1 protein level.These tests are known in the art, and comprise that FISH measures and radioimmunoassay.

Whether having the proteic method of PINX1 in a kind of detection test sample is to utilize the proteic specific antibody of PINX1 to detect, and it comprises: sample is contacted with the PINX1 protein specific antibody; Observe whether form antibody complex, formed antibody complex and just represented to exist in the sample PINX1 albumen.

The proteic polynucleotide of PINX1 can be used for the diagnosis and the treatment of PINX1 protein related diseases.Aspect diagnosis, the proteic polynucleotide of PINX1 can be used for detecting the proteic expression of PINX1 PINX1 abnormal exprssion whether or under morbid state.Can be used for the hybridization of biopsy specimen to judge the proteic abnormal expression of PINX1 as the PINX1 dna sequence dna.Hybridization technique comprises the Southern blotting, Northern blotting, in situ hybridization etc.These technological methods all are disclosed mature technologies, and relevant test kit all can obtain from commercial channels.Part or all of polynucleotide of the present invention can be used as probe stationary on microarray (microarray) or DNA chip (being called " gene chip " again), is used for analyzing the differential expression and the gene diagnosis of tissue gene.Carry out RNA-polymerase chain reaction (RT-PCR) amplification in vitro with the special primer of PINX1 albumen and also can detect the proteic transcription product of PINX1.

The present invention also provides a kind of method of single nucleotide polymorphism of the people of detection PINX1 gene, and it comprises step: (a) determine the 162nd and 367 Nucleotide in sequence shown in the SEQ ID of the people PINX1 gene NO:1; (b) whether detection exists single nucleotide polymorphism (SNP) in described position.Concrete SNP example comprises G162 → A162:C367 → T367.

The sudden change that detects the PINX1 gene also can be used for diagnosing medulloblastoma.Detection can be at cDNA, also can be at genomic dna.The form of PINX1 protein mutation comprises that the point mutation compared with normal wild type PINX1 dna sequence dna, transposition, disappearance, reorganization and other are any unusual etc.Available existing technology such as Southern blotting, dna sequence analysis, PCR and in situ hybridization detect sudden change.In addition, sudden change might influence proteic expression, therefore can judge indirectly that with Northern blotting, Western blotting gene has or not sudden change.

Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, usually according to people such as normal condition such as Sambrook, molecular cloning: laboratory manual (New York:ColdSpring Harbor Laboratory Press, 1989) condition described in, or the condition of advising according to manufacturer.

Embodiment 1 determines that the PINX1 sudden change is the immediate cause that causes medulloblastoma

1.1 object

Collect the paraffin embedding sample and the part patient peripheral blood of 32 routine medulloblastomas.

1.2 pathologic finding

Patient's pathological tissue paraffin section is carried out hematoxylin-eosin staining, and light microscopic is observed down.Institute gets and is cancer cells in the tissue more than 80%.

1.3 individual the evaluation

Utilize 6 pairs of microsatellite polymorphism marks that patient's pathological tissue and peripheral blood are carried out the individuality evaluation.The gene type of patient's pathological tissue and its peripheral blood is in full accord.

1.4 candidate gene screening and detection

After deliberation, will be decided to be an important candidate gene at PIN2 interaction protein 1 (PINX1) on No. 8 the short arm of a chromosome.This gene is expressed in various vital tissues such as brain.

With DNA extraction agent box (Qigen company) extracting genomic dna from paraffin-embedded pathological tissue, with it as template.Nine pairs of primers have been designed and synthesized simultaneously.These primers have covered all exons of this gene, the limit of intron and exon, and the sequence of part operation:

Title	Sequence (5 ' → 3 ')	??SEQ?ID?NO：
			The PINX1-1 forward primer	????5′-CCTCTAGCCAATGAGCGAAT-3′	????5
The PINX1-1 reverse primer	????5′-CGAGCAGGACAATCAGAGC-3′	????6
			The PINX1-2 forward primer	????5′-TGCCACATTATGAGGGAACA-3′	????7
The PINX1-2 reverse primer	????5′-AACAATTTTTGATTTGGGATCA-3′	????8
			The PINX1-3 forward primer	????5′-TGAGTGCTAATTGATGCAGAGG-3′	????9
The PINX1-3 reverse primer	????5′-ACAGTGCCATGCATTCAAAG-3′	????10
			The PINX1-4 forward primer	????5′-CCAGGAAGCCCCTTTTTAAT-3′	????11
The PINX1-4 reverse primer	????5′-TTTTAAATGCTCCCAACACAAA-3′	????12
			The PINX1-5 forward primer	????5′-GCCTGGCCTGATCCATAGTA-3′	????13
The PINX1-5 reverse primer	????5′-CAGTCAATGCGAAGACTCCA-3′	????14
			The PINX1-6 forward primer	????5′-TGAAAAAGTGGGTAGAAAGTCAG-3′	????15
The PINX1-6 reverse primer	????5′-CAAAAGCCAAACACCAGAAAA-3′	????16
			The PINX1-7A forward primer	????5′-CCGACCAGAAGGGAGAGAG-3′	????17
The PINX1-7A reverse primer	????5′-GCTCTTCTTCTTGGCCACTC-3′	????18

The PINX1-7B forward primer	????5′-TCTGAGAGCCACGATTGAGA-3′	????19
			The PINX1-7B reverse primer	????5′GCCACAGGTAAAGATGTGGAA-3′	????20
The PINX1-7C forward primer	????5′-TGAATCCAAGCTATTGCCTCT-3′	????21
			The PINX1-7C reverse primer	????5′-AGGGAAGAAAAAGCTGCAAA-3′	????22

The method of utilizing these nine pairs of primers to adopt pcr amplification, directly check order is carried out the PINX1 detection in Gene Mutation to the medulloblastoma Pathologic specimen.

Through to the PINX1 gene sequencing of 32 routine medulloblastoma pathological tissues and part peripheral blood DNA, find wherein PINX1-2, two pairs of primers of PINX1-4 detect in the pathological tissue PINX1 gene with normally different.It is as follows that full-automatic sequenator detects the sudden change result:

cgcacgtcct?gattctcctg?gagtctccag?cccgcccagt?ggccgcagtc?acccaggtcc??60

agaggcggcg?gtatcacagg?ctctccgaca?tgtctatgct?ggctgaacgt?cggcggaagc??120

agaagtgggc?tgtggatcct?cagaacactg?cctggagtaa?t Gacgattcc?aagtttggcc??180

agcggatgct?agagaagatg?gggtggtcta?aaggaaaggg?tttaggggct?caggagcacg??240

gagccacaga?tcatattaaa?gttcaagtga?aaaataacca?cctgggactc?ggagctacca??300

tcaataatga?agacaactgg?attgcccatc?aggatgattt?taaccagctt?ctggccgaac??360

tgaaca Cttg?ccatgggcag?gaaaccacag?attcctcgga?caagaaggaa?aagaaatctt??420

ttagccttga?ggaaaagtcc?aaaatctcca?aaaaccgtgt?tcactatatg?aaattcacaa??480

aagggaagga?tctgtcatct?cggagcaaaa?cagatcttga?ctgcattttt?gggaaaagac??540

agagtaagaa?gactcccgag?ggcgatgcca?gtccctccac?tccagaggag?aacgaaacca??600

cgacaaccag?cgccttcacc?atccaggagt?actttgccaa?gcggatggca?gcactgaaga??660

acaagcccca?ggttccagtt?ccagggtctg?acatttctga?gacgcaggtg?gaacgtaaaa??720

gggggaagaa?aataaataaa?gaggccacag?gtaaagatgt?ggaaagttac?ctccagccta??780

aggccaagag?gcacacggag?ggaaagcccg?agagggccga?ggcccaggag?cgagtggcca??840

agaagaagag?cgcgccagca?gaagagcagc?tcagaggccc?ctgctgggac?cagagttcca??900

aggcctctgc?tcaggatgca?ggggaccatg?tgcagccgcc?tgagggccgg?gacttcaccc??960

tgaagcccaa?aaagaggaga?gggaagaaaa?agctgcaaaa?accagtagag?atagcagagg??1020

acgctacact?agaagaaacg?ctagtgaaaa?agaagaagaa?gaaagattcc?aaatgaatcc??1080

ttcccagccg?gggccttccg?accactcagc?tgtcagggca?ctgcgggggc?agacacctct??1140

ggcctgaagt?cacagcagag?ttcaccccag?agcgcctggg?cgcatcttgt?ggcatgccca??1200

tgggctgccg?agtcctgccc?tctcgccaca?tttcccccaa?gttacattcc?caggaggacc??1260

tttttaatgt?tctcaatcgt?ggctctcaga?cacaaataaa?tttttttgta?aactctgaaa??1320

aaaaaaaaaa?aa??????????????????????????????????????????????????????1332

(SEQ?ID?NO：1)

As implied above, normal people's sequence " ... aatGacg ... " in 1 routine medulloblastoma pathological tissue, isozygoty and be changed to " ... aatAacg ... " this variation has directly caused among its coded product SEQ ID NO:2 the 25th to become l-asparagine (N) (exon 2 by aspartic acid (D), G162 → A162 of the 162nd sees Figure 1A in the mRNA encoding sequence).

Normal people's sequence " ... acaCttg ... " in 1 routine medulloblastoma pathological tissue, isozygoty and change into " ... acaTttg ... " this variation has directly caused among its coded product SEQ ID NO:2 the 93rd to become Isoleucine (I) (exon 4 by Threonine (T), C367 → T367 of the 367th sees Figure 1B in the mRNA encoding sequence).

The PINX1 sequence that contains G162 → A162 and C367 → T367 sudden change (SNP) is shown in SEQ IDNO:3, and the aminoacid sequence of the mutain of its coding is shown in SEQ ID NO:4.Should point out that these sequences have been represented and contained G162 → A162 and/or C367 → T367 sudden change, and the sequence that contains Asp25 → Asn25 and/or Thr93 → Ile93 sudden change.

In addition, for the specificity of verifying that the mutational site takes place medulloblastoma, casual inspection 300 situations that do not have the people of close source relation in described site, do not find not have any sudden change.This illustrates that described site mutation is not due to the polymorphism among the crowd, but the specific mutant site of medulloblastoma.Therefore shown that PINX1 is closely related with the generation of the mankind's medulloblastoma, this gene and coded product thereof can play an important role to the mankind's medulloblastoma.

1.5 the allele heterozygosity of PINX1 gene disappearance (LOH)

The microsatellite polymorphism mark D8S1130 that utilization is positioned at the 8P22 site carries out gene type to patient's pathological tissue and the peripheral blood that G162 → A162 sudden change takes place, and finds the allele heterozygosity deficient phenomena.In addition, the sequencing result of this patient's Pathologic specimen PINX1 gene extron 3 has further proved exist (the seeing Fig. 1 C) of LOH.

Discuss

The somatocyte homozygosity sudden change of G162 → A162 makes PINX1 albumen become l-asparagine (N) at 25 by aspartic acid (D).To this sequence of 300 normal peoples relatively in, all do not find this variation.Structure prediction shows that this zone is the proteic phosphorylation site of PINX1, and aspartic acid may influence the normal formation of albumen secondary structure to the variation of l-asparagine.In addition, through comparing with other species homology, the amino acid of this sudden change place has high conservative, and is positioned at crucial G-PATH fringe region, and pointing out 25 aspartic acid is the basis of keeping protein function.In addition, this gene type to sample 8P22 site microsatellite polymorphism mark D8S1130 is presented at and has allelic heterozygosity disappearance (LOH) in the pathological tissue.The sequencing result of pathology sample P INX1 gene extron 3 has also further confirmed the appearance of LOH.

The homozygous mutation of C367 → T367 on the PINX1 mRNA has directly caused its coded product 93 sites to become Isoleucine (I) by Threonine (T).This site presents conservative property in mouse, also do not occur identical change 300 normal people PINX1 sequences in relatively, points out 93 Threonine to play an important role to keeping proteic function.

In a word, the present invention disclose first PIN2 interaction protein 1 (PINX1) and human cancer particularly medulloblastoma generation and develop closely related, this gene and coded product thereof to the mankind's cancer particularly medulloblastoma play an important role.

In addition, No. 8 the short arm of a chromosome are hot spot regions that heterozygosity disappearance (LOH) takes place in many cancers and the tumor tissues.This strong prompting exists the cancer suppressor gene that plays a significant role herein in all kinds of tumours and cancer.PINX1 is positioned in this zone just.Existing studies show that, this gene and cell Telomerase vigor and apoptosis-related have hinted that itself and cancer, tumour take place and the dependency of development.

The present invention has disclosed PINX1 first and medulloblastoma is closely related, and its change will promote the generation and the development of medulloblastoma.Because the PINX1 gene all has than high expression level in numerous human body vital tissues such as heart, brain, kidney, lung, stomach, liver, pancreas, prostate gland, ovary, skin, uterus, esophagus, muscle, the scope of expressing has widely confirmed the importance of this gene from another side, and the afunction of hint PINX1 is to cause one of the multiple cancer except that medulloblastoma, immediate cause of tumour.These cancers comprise (but being not limited to): cancer of the stomach, lung cancer, liver cancer, prostate cancer, mammary cancer, colorectal carcinoma, carcinoma of the pancreas, bladder cancer etc.

Embodiment 3

The preparation of medulloblastoma diagnostic test kits

Prepare a test kit, it contains:

Title	Sequence (5 ' → 3 ')	Numbering	Concentration
				The PINX1-2 forward primer	????tgccacattatgagggaaca	SEQ?ID?NO：7	Dry powder 20D
The PINX1-2 reverse primer	????aacaatttttgatttgggatca	SEQ?ID?NO：8	Dry powder 20D
				Expanding fragment length: 504bp detects sudden change G162 → A162
The PINX1-4 forward primer	????ccaggaagcccctttttaat	SEQ?ID?NO：11	Dry powder 20D
				The PINX1-4 reverse primer	????ttttaaatgctcccaacacaaa	SEQ?ID?NO：12	Dry powder 20D
Expanding fragment length: 520bp detects C367 → T367 sudden change
				The PCR reaction solution	Contain Taq enzyme dNTP magnesium ion PCR reaction buffer
PCR product purification box	Contain the solution of PCR product purification in a small amount, the DNA adsorption column
				Sequencing reaction liquid	Contain Big Dye

Extract patients'blood 3ml to be detected or tumor tissues 20-30mg, use ordinary method (or using specific test kit) from blood or tissue, to extract DNA.PCR primer in the medulloblastoma detection kit is diluted to 1 μ mol/ μ l, is that template is carried out the PCR reaction with the primer that is provided with the DNA that is extracted.Use the PRC product purification box that detection kit provided that the PCR product is carried out purifying.The product of purifying is carried out directly checking order behind the sequencing reaction.Observe resulting extension increasing sequence whether have point mutation G162 → A162 and/or C367 → T367.

Embodiment 4

Preparation of drug combination

The normal protein that PINX1 is coded is mixed with injection with the medical buffer soln of routine, and wherein the PINX1 protein content is 0.5%.This injection can replenish the PINX1 proteins encoded of affected area, and patient's physiological situation is improved, thereby reaches the purpose of treatment.

All quote in this application as a reference at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.

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3.Yin?XL，Pang?JC，Ng?HK.(2002).Identification?of?a?region?of?homozygousdeletion?on?8p22-8p23.1?in?medulloblastoma.Oncogene?21：1461-1468.

4.Zhou?XZ，Lu?KP.(2001).The?Pin2/TRFl-interacting?protein?PinX1?is?a?potenttelomerase?inhibitor.Cell?107：347-359.

Sequence table＜110〉Shanghai Research Center of Biotechnology＜120〉cancer suppressor gene PINX 1 and application＜130 thereof〉023583＜160〉22＜170〉PatentIn version 3.1＜210〉1＜211〉1332＜212〉DNA＜213〉homo sapiens (Homo sapiens)＜220〉＜221〉CDS＜222〉(90) .. (1073)＜223〉＜400〉1cgcacgtcct gattctcctg gagtctccag cccgcccagt ggccgcagtc acccaggtcc 60agaggcggcg gtatcacagg ctctccgac atg tct atg ctg gct gaa cgt cgg 113

Met?Ser?Met?Leu?Ala?Glu?Arg?Arg

1???????????????5cgg?aag?cag?aag?tgg?gct?gtg?gat?cct?cag?aac?act?gcc?tgg?agt?aat???????161Arg?Lys?Gln?Lys?Trp?Ala?Val?Asp?Pro?Gln?Asn?Thr?Ala?Trp?Ser?Asn

10??????????????????15??????????????????20gac?gat?tcc?aag?ttt?ggc?cag?cgg?atg?cta?gag?aag?atg?ggg?tgg?tct???????209Asp?Asp?Ser?Lys?Phe?Gly?Gln?Arg?Met?Leu?Glu?Lys?Met?Gly?Trp?Ser25??????????????????30??????????????????35??????????????????40aaa?gga?aag?ggt?tta?ggg?gct?cag?gag?cac?gga?gcc?aca?gat?cat?att???????257Lys?Gly?Lys?Gly?Leu?Gly?Ala?Gln?Glu?His?Gly?Ala?Thr?Asp?His?Ile

45??????????????????50??????????????????55aaa?gtt?caa?gtg?aaa?aat?aac?cac?ctg?gga?ctc?gga?gct?acc?atc?aat???????305Lys?Val?Gln?Val?Lys?Asn?Asn?His?Leu?Gly?Leu?Gly?Ala?Thr?Ile?Asn

60??????????????????65??????????????????70aat?gaa?gac?aac?tgg?att?gcc?cat?cag?gat?gat?ttt?aac?cag?ctt?ctg???????353Asn?Glu?Asp?Asn?Trp?Ile?Ala?His?Gln?Asp?Asp?Phe?Asn?Gln?Leu?Leu

75??????????????????80??????????????????85gcc?gaa?ctg?aac?act?tgc?cat?ggg?cag?gaa?acc?aca?gat?tcc?tcg?gac???????401Ala?Glu?Leu?Asn?Thr?Cys?His?Gly?Gln?Glu?Thr?Thr?Asp?Ser?Ser?Asp

90??????????????????95??????????????????100aag?aag?gaa?aag?aaa?tct?ttt?agc?ctt?gag?gaa?aag?tcc?aaa?atc?tcc??????449Lys?Lys?Glu?Lys?Lys?Ser?Phe?Ser?Leu?Glu?Glu?Lys?Ser?Lys?Ile?Ser105?????????????????110?????????????????115?????????????????120aaa?aac?cgt?gtt?cac?tat?atg?aaa?ttc?aca?aaa?ggg?aag?gat?ctg?tca??????497Lys?Asn?Arg?Val?His?Tyr?Met?Lys?Phe?Thr?Lys?Gly?Lys?Asp?Leu?Ser

125?????????????????130?????????????????135tct?cgg?agc?aaa?aca?gat?ctt?gac?tgc?att?ttt?ggg?aaa?aga?cag?agt??????545Ser?Arg?Ser?Lys?Thr?Asp?Leu?Asp?Cys?Ile?Phe?Gly?Lys?Arg?Gln?Ser

140?????????????????145?????????????????150aag?aag?act?ccc?gag?ggc?gat?gcc?agt?ccc?tcc?act?cca?gag?gag?aac??????593Lys?Lys?Thr?Pro?Glu?Gly?Asp?Ala?Ser?Pro?Ser?Thr?Pro?Glu?Glu?Asn

155?????????????????160?????????????????165gaa?acc?acg?aca?acc?agc?gcc?ttc?acc?atc?cag?gag?tac?ttt?gcc?aag??????641Glu?Thr?Thr?Thr?Thr?Ser?Ala?Phe?Thr?Ile?Gln?Glu?Tyr?Phe?Ala?Lys

170?????????????????175?????????????????180cgg?atg?gca?gca?ctg?aag?aac?aag?ccc?cag?gtt?cca?gtt?cca?ggg?tct??????689Arg?Met?Ala?Ala?Leu?Lys?Asn?Lys?Pro?Gln?Val?Pro?Val?Pro?Gly?Ser185?????????????????190?????????????????195?????????????????200gac?att?tct?gag?acg?cag?gtg?gaa?cgt?aaa?agg?ggg?aag?aaa?ata?aat??????737Asp?Ile?Ser?Glu?Thr?Gln?Val?Glu?Arg?Lys?Arg?Gly?Lys?Lys?Ile?Asn

205?????????????????210?????????????????215aaa?gag?gcc?aca?ggt?aaa?gat?gtg?gaa?agt?tac?ctc?cag?cct?aag?gcc??????785Lys?Glu?Ala?Thr?Gly?Lys?Asp?Val?Glu?Ser?Tyr?Leu?Gln?Pro?Lys?Ala

220?????????????????225?????????????????230aag?agg?cac?acg?gag?gga?aag?ccc?gag?agg?gcc?gag?gcc?cag?gag?cga??????833Lys?Arg?His?Thr?Glu?Gly?Lys?Pro?Glu?Arg?Ala?Glu?Ala?Gln?Glu?Arg

235?????????????????240?????????????????245gtg?gcc?aag?aag?aag?agc?gcg?cca?gca?gaa?gag?cag?ctc?aga?ggc?ccc??????881Val?Ala?Lys?Lys?Lys?Ser?Ala?Pro?Ala?Glu?Glu?Gln?Leu?Arg?Gly?Pro

250?????????????????255?????????????????260tgc?tgg?gac?cag?agt?tcc?aag?gcc?tct?gct?cag?gat?gca?ggg?gac?cat??????929Cys?Trp?Asp?Gln?Ser?Ser?Lys?Ala?Ser?Ala?Gln?Asp?Ala?Gly?Asp?His265?????????????????270?????????????????275?????????????????280gtg?cag?ccg?cct?gag?ggc?cgg?gac?ttc?acc?ctg?aag?ccc?aaa?aag?agg??????977Val?Gln?Pro?Pro?Glu?Gly?Arg?Asp?Phe?Thr?Leu?Lys?Pro?Lys?Lys?Arg

285?????????????????290?????????????????295aga?ggg?aag?aaa?aag?ctg?caa?aaa?cca?gta?gag?ata?gca?gag?gac?gct?????1025Arg?Gly?Lys?Lys?Lys?Leu?Gln?Lys?Pro?Val?Glu?Ile?Ala?Glu?Asp?Ala

300?????????????????305?????????????????310aca?cta?gaa?gaa?acg?cta?gtg?aaa?aag?aag?aag?aag?aaa?gat?tcc?aaa?????1073Thr?Leu?Glu?Glu?Thr?Leu?Val?Lys?Lys?Lys?Lys?Lys?Lys?Asp?Ser?Lys

315 320 325tgaatccttc ccagccgggg ccttccgacc actcagctgt cagggcactg cgggggcaga 1133cacctctggc ctgaagtcac agcagagttc accccagagc gcctgggcgc atcttgtggc 1193atgcccatgg gctgccgagt cctgccctct cgccacattt cccccaagtt acattcccag 1253gaggaccttt ttaatgttct caatcgtggc tctcagacac aaataaattt ttttgtaaac 1313tctgaaaaaa aaaaaaaaa, 1332＜210〉2＜21l〉328＜212〉PRT＜213〉homo sapiens (Homo sapiens)＜400〉2Met Ser Met Leu Ala Glu Arg Arg Arg Lys Gln Lys Trp Ala Val Asp1,5 10 15Pro Gln Asn Thr Ala Trp Ser Asn Asp Asp Ser Lys Phe Gly Gln Arg

20??????????????????25??????????????????30Met?Leu?Glu?Lys?Met?Gly?Trp?Ser?Lys?Gly?Lys?Gly?Leu?Gly?Ala?Gln

35??????????????????40??????????????????45Glu?His?Gly?Ala?Thr?Asp?His?Ile?Lys?Val?Gln?Val?Lys?Asn?Asn?His

50??????????????????55??????????????????60Leu?Gly?Leu?Gly?Ala?Thr?Ile?Asn?Asn?Glu?Asp?Asn?Trp?Ile?Ala?His65??????????????????70??????????????????75??????????????????80Gln?Asp?Asp?Phe?Asn?Gln?Leu?Leu?Ala?Glu?Leu?Asn?Thr?Cys?His?Gly

85??????????????????90??????????????????95Gln?Glu?Thr?Thr?Asp?Ser?Ser?Asp?Lys?Lys?Glu?Lys?Lys?Ser?Phe?Ser

100?????????????????105?????????????????110Leu?Glu?Glu?Lys?Ser?Lys?Ile?Ser?Lys?Asn?Arg?Val?His?Tyr?Met?Lys

115?????????????????120?????????????????125Phe?Thr?Lys?Gly?Lys?Asp?Leu?Ser?Ser?Arg?Ser?Lys?Thr?Asp?Leu?Asp

130?????????????????135?????????????????140Cys?Ile?Phe?Gly?Lys?Arg?Gln?Ser?Lys?Lys?Thr?Pro?Glu?Gly?Asp?Ala145?????????????????150?????????????????155?????????????????160Ser?Pro?Ser?Thr?Pro?Glu?Glu?Asn?Glu?Thr?Thr?Thr?Thr?Ser?Ala?Phe

165?????????????????170?????????????????175Thr?Ile?Gln?Glu?Tyr?Phe?Ala?Lys?Arg?Met?Ala?Ala?Leu?Lys?Asn?Lys

180?????????????????185?????????????????190Pro?Gln?Val?Pro?Val?Pro?Gly?Ser?Asp?Ile?Ser?Glu?Thr?Gln?Val?Glu

195?????????????????200?????????????????205Arg?Lys?Arg?Gly?Lys?Lys?Ile?Asn?Lys?Glu?Ala?Thr?Gly?Lys?Asp?Val

210?????????????????215?????????????????220Glu?Ser?Tyr?Leu?Gln?Pro?Lys?Ala?Lys?Arg?His?Thr?Glu?Gly?Lys?Pro225?????????????????230?????????????????235?????????????????240Glu?Arg?Ala?Glu?Ala?Gln?Glu?Arg?Val?Ala?Lys?Lys?Lys?Ser?Ala?Pro

245?????????????????250?????????????????255Ala?Glu?Glu?Gln?Leu?Arg?Gly?Pro?Cys?Trp?Asp?Gln?Ser?Ser?Lys?Ala

260?????????????????265?????????????????270Ser?Ala?Gln?Asp?Ala?Gly?Asp?His?Val?Gln?Pro?Pro?Glu?Gly?Arg?Asp

275?????????????????280?????????????????285Phe?Thr?Leu?Lys?Pro?Lys?Lys?Arg?Arg?Gly?Lys?Lys?Lys?Leu?Gln?Lys

290?????????????????295?????????????????300Pro?Val?Glu?Ile?Ala?Glu?Asp?Ala?Thr?Leu?Glu?Glu?Thr?Leu?Val?Lys305?????????????????310?????????????????315?????????????????320Lys?Lys?Lys?Lys?Lys?Asp?Ser?Lys

325＜210〉3＜211〉1332＜212〉DNA＜213〉homo sapiens (Homo sapiens)＜220〉＜221〉CDS＜222〉(90) .. (1073)＜223〉＜400〉3cgcacgtcct gattctcctg gagtctccag cccgcccagt ggccgcagtc acccaggtcc 60agaggcggcg gtatcacagg ctctccgac atg tct atg ctg gct gaa cgt cgg 113

Met?Ser?Met?Leu?Ala?Glu?Arg?Arg

1???????????????5cgg?aag?cag?aag?tgg?gct?gtg?gat?cct?cag?aac?act?gcc?tgg?agt?aat??????161Arg?Lys?Gln?Lys?Trp?Ala?Val?Asp?Pro?Gln?Asn?Thr?Ala?Trp?Set?Asn

10??????????????????15??????????????????20aac?gat?tcc?aag?ttt?ggc?cag?cgg?atg?cta?gag?aag?atg?ggg?tgg?tct??????209Asn?Asp?Ser?Lys?Phe?Gly?Gln?Arg?Met?Leu?Glu?Lys?Met?Gly?Trp?Ser25??????????????????30??????????????????35??????????????????40aaa?gga?aag?ggt?tta?ggg?gct?cag?gag?cac?gga?gcc?aca?gat?cat?att??????257Lys?Gly?Lys?Gly?Leu?Gly?Ala?Gln?Glu?His?Gly?Ala?Thr?Asp?His?Ile

45??????????????????50??????????????????55aaa?gtt?caa?gtg?aaa?aat?aac?cac?ctg?gga?crc?gga?gct?acc?atc?aat??????305Lys?Val?Gln?Val?Lys?Asn?Ash?His?Leu?Gly?Leu?Gly?Ala?Thr?Ile?Asn

60??????????????????65??????????????????70aat?gaa?gac?aac?tgg?att?gcc?cat?cag?gat?gat?ttt?aac?cag?ctt?ctg??????353Asn?Glu?Asp?Asn?Trp?Ile?Ala?His?Gln?Asp?Asp?Phe?Asn?Gln?Leu?Leu

75??????????????????80??????????????????85gcc?gaa?ctg?aac?att?tgc?cat?ggg?cag?gaa?acc?aca?gat?tcc?tcg?gac??????401Ala?Glu?Leu?Asn?Ile?Cys?His?Gly?Gln?Glu?Thr?Thr?Asp?Set?Ser?Asp

90??????????????????95??????????????????100aag?aag?gaa?aag?aaa?tct?ttt?agc?ctt?gag?gaa?aag?tcc?aaa?arc?tcc??????449Lys?Lys?Glu?Lys?Lys?Ser?Phe?Ser?Leu?Glu?Glu?Lys?Ser?Lys?Ile?Ser105?????????????????110?????????????????115?????????????????120aaa?aac?cgt?gtt?cac?tat?atg?aaa?ttc?aca?aaa?ggg?aag?gat?ctg?tca??????497Lys?Asn?Arg?Val?His?Tyr?Met?Lys?Phe?Thr?Lys?Gly?Lys?Asp?Leu?Ser

125?????????????????130?????????????????135tct?cgg?agc?aaa?aca?gat?ctt?gac?tgc?att?ttt?ggg?aaa?aga?cag?agt??????545Ser?Arg?Ser?Lys?Thr?Asp?Leu?Asp?Cys?Ile?Phe?Gly?Lys?Arg?Gln?Ser

140?????????????????145?????????????????150aag?aag?act?ccc?gag?ggc?gat?gcc?agt?ccc?tcc?act?cca?gag?gag?aac??????593Lys?Lys?Thr?Pro?Glu?Gly?Asp?Ala?Ser?Pro?Ser?Thr?Pro?Glu?Glu?Asn

155?????????????????160?????????????????165gaa?acc?acg?aca?acc?agc?gcc?ttc?acc?atc?cag?gag?tac?ttt?gcc?aag??????641Glu?Thr?Thr?Thr?Thr?Ser?Ala?Phe?Thr?Ile?Gln?Glu?Tyr?Phe?Ala?Lys

170?????????????????175?????????????????180cgg?atg?gca?gca?ctg?aag?aac?aag?ccc?cag?gtt?cca?gtt?cca?ggg?tct??????689Arg?Met?Ala?Ala?Leu?Lys?Asn?Lys?Pro?Gln?Val?Pro?Val?Pro?Gly?Ser185?????????????????190?????????????????195?????????????????200gac?att?tct?gag?acg?cag?gtg?gaa?cgt?aaa?agg?ggg?aag?aaa?ata?aat??????737Asp?Ile?Ser?Glu?Thr?Gln?Val?Glu?Arg?Lys?Arg?Gly?Lys?Lys?Ile?Asn

205?????????????????210?????????????????215aaa?gag?gcc?aca?ggt?aaa?gat?gtg?gaa?agt?tac?ctc?cag?cct?aag?gcc??????785Lys?Glu?Ala?Thr?Gly?Lys?Asp?Val?Glu?Ser?Tyr?Leu?Gln?Pro?Lys?Ala

220?????????????????225?????????????????230aag?agg?cac?acg?gag?gga?aag?ccc?gag?agg?gcc?gag?gcc?cag?gag?cga??????833Lys?Arg?His?Thr?Glu?Gly?Lys?Pro?Glu?Arg?Ala?Glu?Ala?Gln?Glu?Arg

235?????????????????240?????????????????245gtg?gcc?aag?aag?aag?agc?gcg?cca?gca?gaa?gag?cag?ctc?aga?ggc?ccc??????881Val?Ala?Lys?Lys?Lys?Ser?Ala?Pro?Ala?Glu?Glu?Gln?Leu?Arg?Gly?Pro

250?????????????????255?????????????????260tgc?tgg?gac?cag?agt?tcc?aag?gcc?tct?gct?cag?gat?gca?ggg?gac?cat??????929Cys?Trp?Asp?Gln?Ser?Ser?Lys?Ala?Ser?Ala?Gln?Asp?Ala?Gly?Asp?His265?????????????????270?????????????????275?????????????????280gtg?cag?ccg?cct?gag?ggc?cgg?gac?ttc?acc?ctg?aag?ccc?aaa?aag?agg??????977Val?Gln?Pro?Pro?Glu?Gly?Arg?Asp?Phe?Thr?Leu?Lys?Pro?Lys?Lys?Arg

285?????????????????290?????????????????295aga?ggg?aag?aaa?aag?ctg?caa?aaa?cca?gta?gag?ata?gca?gag?gac?gct?????1025Arg?Gly?Lys?Lys?Lys?Leu?Gln?Lys?Pro?Val?Glu?Ile?Ala?Glu?Asp?Ala

300?????????????????305?????????????????310aca?cta?gaa?gaa?acg?cta?gtg?aaa?aag?aag?aag?aag?aaa?gat?tcc?aaa?????1073Thr?Leu?Glu?Glu?Thr?Leu?Val?Lys?Lys?Lys?Lys?Lys?Lys?Asp?Ser?Lys

315 320 325tgaatccttc ccagccgggg ccttccgacc actcagctgt cagggcactg cgggggcaga 1133cacctctggc ctgaagtcac agcagagttc accccagagc gcctgggcgc atcttgtggc 1193atgcccatgg gctgccgagt cctgccctct cgccacattt cccccaagtt acattcccag 1253gaggaccttt ttaatgttct caatcgtggc tctcagacac aaataaattt ttttgtaaac 1313tctgaaaaaa aaaaaaaaa, 1332＜210〉4＜211〉328＜212〉PRT＜213〉homo sapiens (Homo sapiens)＜400〉4Met Ser Met Leu Ala Glu Arg Arg Arg Lys Gln Lys Trp Ala Val Asp1,5 10 15Pro Gln Asn Thr Ala Trp Ser Asn Asn Asp Ser Lys Phe Gly Gln Arg

20??????????????????25??????????????????30Met?Leu?Glu?Lys?Met?Gly?Trp?Ser?Lys?Gly?Lys?Gly?Leu?Gly?Ala?Gln

35??????????????????40??????????????????45Glu?His?Gly?Ala?Thr?Asp?His?Ile?Lys?Val?Gln?Val?Lys?Asn?Asn?His

50??????????????????55??????????????????60Leu?Gly?Leu?Gly?Ala?Thr?Ile?Asn?Asn?Glu?Asp?Asn?Trp?Ile?Ala?His65??????????????????70??????????????????75??????????????????80Gln?Asp?Asp?Phe?Asn?Gln?Leu?Leu?Ala?Glu?Leu?Asn?Ile?Cys?His?Gly

85??????????????????90??????????????????95Gln?Glu?Thr?Thr?Asp?Ser?Ser?Asp?Lys?Lys?Glu?Lys?Lys?Ser?Phe?Ser

100?????????????????105?????????????????110Leu?Glu?Glu?Lys?Ser?Lys?Ile?Ser?Lys?Asn?Arg?Val?His?Tyr?Met?Lys

115?????????????????120?????????????????125Phe?Thr?Lys?Gly?Lys?Asp?Leu?Ser?Ser?Arg?Ser?Lys?Thr?Asp?Leu?Asp

130?????????????????135?????????????????140Cys?Ile?Phe?Gly?Lys?Arg?Gln?Ser?Lys?Lys?Thr?Pro?Glu?Gly?Asp?Ala145?????????????????150?????????????????155?????????????????160Ser?Pro?Ser?Thr?Pro?Glu?Glu?Asn?Glu?Thr?Thr?Thr?Thr?Ser?Ala?Phe

165?????????????????170?????????????????175Thr?Ile?Gln?Glu?Tyr?Phe?Ala?Lys?Arg?Met?Ala?Ala?Leu?Lys?Asn?Lys

180?????????????????185?????????????????190Pro?Gln?Val?Pro?Val?Pro?Gly?Ser?Asp?Ile?Ser?Glu?Thr?Gln?Val?Glu

195?????????????????200?????????????????205Arg?Lys?Arg?Gly?Lys?Lys?Ile?Asn?Lys?Glu?Ala?Thr?Gly?Lys?Asp?Val

210?????????????????215?????????????????220Glu?Ser?Tyr?Leu?Gln?Pro?Lys?Ala?Lys?Arg?His?Thr?Glu?Gly?Lys?Pro225?????????????????230?????????????????235?????????????????240Glu?Arg?Ala?Glu?Ala?Gln?Glu?Arg?Val?Ala?Lys?Lys?Lys?Ser?Ala?Pro

245?????????????????250?????????????????255Ala?Glu?Glu?Gln?Leu?Arg?Gly?Pro?Cys?Trp?Asp?Gln?Ser?Ser?Lys?Ala

260?????????????????265?????????????????270Ser?Ala?Gln?Asp?Ala?Gly?Asp?His?Val?Gln?Pro?Pro?Glu?Gly?Arg?Asp

275?????????????????280?????????????????285Phe?Thr?Leu?Lys?Pro?Lys?Lys?Arg?Arg?Gly?Lys?Lys?Lys?Leu?Gln?Lys

290?????????????????295?????????????????300Pro?Val?Glu?Ile?Ala?Glu?Asp?Ala?Thr?Leu?Glu?Glu?Thr?Leu?Val?Lys305?????????????????310?????????????????315?????????????????320Lys?Lys?Lys?Lys?Lys?Asp?Ser?Lys

325＜210〉5＜211〉20＜212〉DNA＜213〉＜400〉5cctctagcca atgagcgaat 20＜210〉6＜211〉19＜212〉DNA＜213〉＜400〉6cgagcaggac aatcagagc 19＜210〉7＜211〉20＜212〉DNA＜213〉＜400〉7tgccacatta tgagggaaca 20＜210〉8＜211〉22＜212〉DNA＜213〉＜400〉8aacaattttt gatttgggat ca 22＜210〉9＜211〉22＜212〉DNA＜213〉＜400〉9tgagtgctaa ttgatgcaga gg 22＜210〉10＜211〉20＜212〉DNA＜213〉＜400〉10acagtgccat gcattcaaag 20＜210〉11＜211〉20＜212〉DNA＜213〉＜400〉11ccaggaagcc cctttttaat 20＜210〉12＜211〉22＜212〉DNA＜213〉＜400〉12ttttaaatgc tcccaacaca aa 22＜210〉13＜211〉20＜212〉DNA＜213〉＜400〉13gcctggcctg atccatagta 20＜210〉14＜211〉20＜212〉DNA＜213〉＜400〉14cagtcaatgc gaagactcca 20＜210〉15＜211〉23＜212〉DNA＜213〉＜400〉15tgaaaaagtg ggtagaaagt cag 23＜210〉16＜211〉21＜212〉DNA＜213〉＜400〉16caaaagccaa acaccagaaa a 21＜210〉17＜211〉19＜212〉DNA＜213〉＜400〉17ccgaccagaa gggagagag 19＜210〉18＜211〉20＜212〉DNA＜213〉＜400〉18gctcttcttc ttggccactc 20＜210〉19＜211〉20＜212〉DNA＜213〉＜400〉19tctgagagcc acgattgaga 20＜210〉20＜211〉21＜212〉DNA＜213〉＜400〉20gccacaggta aagatgtgga a 21＜210〉21＜211〉21＜212〉DNA＜213〉＜400〉21tgaatccaag ctattgcctc t 21＜210〉22＜211〉20＜212〉DNA＜213〉＜400〉22agggaagaaa aagctgcaaa 20

Claims (10)

1. method that the cancer susceptibility of individuality is diagnosed is characterized in that it comprises step:

Detect this individual PINX1 gene, transcript and/or albumen, and compare with normal PINX1 gene, transcript and/or albumen,

There are differences and just show that the cancered possibility of this individuality is higher than normal population.

2. the method for claim 1 is characterized in that, described cancer is a medulloblastoma, and what detect is gene or the transcript of PINX1, and with normal PINX1 nucleotide sequence comparing difference.

3. the method for claim 1 is characterized in that, described difference is selected from down group:

The 162nd G162 becomes A162 among the SEQ ID NO:1; With

The 367th C367 becomes T367 among the SEQ ID NO:1.

4. a treatment method for cancer is characterized in that, comprises step: the normal PINX1 albumen to the patient of the described treatment of needs uses safe and effective amount perhaps with normal PINX1 gene target importing tumor tissues, expresses it in tumour cell.

5. method as claimed in claim 4 is characterized in that described cancer is a medulloblastoma, and described PINX1 albumen is applied to tumor tissues.

6. a pharmaceutical composition is characterized in that, it contains the PINX1 albumen and the pharmaceutically acceptable carrier of significant quantity.

7. a test kit that detects cancer is characterized in that, it comprises the primer of specific amplification PINX1 gene or transcript.

8. test kit as claimed in claim 7 is characterized in that described cancer is a medulloblastoma, and described test kit also contains and mutable site bonded probe.

9. test kit as claimed in claim 8 is characterized in that, described sudden change is selected from:

The 162nd G162 becomes A162 among the SEQ ID NO:1;

The 367th C367 becomes T367 among the SEQ ID NO:1.

10. method that detects the single nucleotide polymorphism of people PINX1 gene is characterized in that it comprises step:

(a) determine the 162nd and 367 Nucleotide in sequence shown in the SEQ ID of the people PINX1 gene NO:1; With

(b) whether detection exists single nucleotide polymorphism G 162 → A162 and the C367 → T367 that is selected from following group in described position.

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