| Identity |
| Other names | MMAC1 (Mutated in Multiple Advanced Cancer 1) |
| TEP 1 (TGFb regulated and Epithelial cell enriched Phosphatase 1) | |
| HGNC (Hugo) | PTEN |
| LocusID (NCBI) | 5728 |
| Location | 10q23.31 |
| Location_base_pair | Starts at 89623195 and ends at 89728532 bp from pter ( according to hg19-Feb_2009) [Mapping] |
| Local_order | between D10S1765 and D10S541 |
| DNA/RNA |
| Description | 9 exons, all coding; exon 1 has an unusually long 5' untranslated GC-rich region; exon 5 codes for the phosphatase core motif |
| Transcription | 2 major detected transcripts; respectively 2 and 5 kb; open reading frame : 1209 bp |
| Protein |
| Description | 403 aminoacids, 47 kDa; N-terminal phosphatase domain (from a.a. 1 to 185) with the catalytic core motif between; a.a. 123-131 encoded by exon 5; C-terminal PDZ binding domain |
| Localisation | cytoplasmic localization (immunohistochemistry) |
| Function | phosphatase activity; substrate : phosphatidylinositol 3,4,5-tri phosphate (PIP3); PTEN appears as a negative regulator of the PI3K/AKT signaling pathway; It is unclear if PTEN is able to dephosphorylate a protein substrate in vivo; tumor suppressive function: biallelic inactivation is observed in several tumor-types and inactivating germline mutations are responsible for a cancer prone syndrome, the Cowden disease; anti-invasive and anti-proliferative effects were documented in several cell lines |
| Mutations |
| Germinal | germline mutations have been documented in Cowden disease and in Bannayan, Riley, Ruvalcaba phenotype (see below); they are observed along the various exons of the gene except the 9th (never described) and the 1st (very few reports); a mutational hot spot is observed in exon 5 in relation with the catalytic core motif; in the great majority of the cases, inactivating mutations are observed, either by protein truncation, or by misense mutation within the phosphatase domain |
| Somatic | mutations are observed in several tumor type; they lead to a biallelic inactivation of the gene either by homozygous deletion, or by a combination of point mutation and a large deletion of the second allele |
| Implicated in |
| Entity | Cowden disease and Bannayan, Riley, Ruvalcaba phenotype |
| Disease | Cowden disease is also known as multiple hamartoma syndrome, a cancer prone condition with autosomal dominant pattern of inheritance and high susceptibility to breast carcinoma and in a less extent to thyroid carcinoma; Bannayan, Ryley, Ruvalcaba syndrome correspond to the pediatric contrepart of Cowden disease with phenotypic overlap between the 2 syndromes (macrocephaly, intestinal polyps, lipomas, genital pigmented macules) |
| Entity | sporadic malignant tumors |
| Disease | somatic mutations were observed mainly in glioblastoma and in endometrial carcinoma, about 30% of these two kinds of tumors showing point mutations; only a few mutations were reported in prostate carcinoma, malignant melanoma, non Hodgkin lymphomas, breast carcinoma |
| External links |
| Bibliography |
| PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. |
| Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R |
| Science (New York, N.Y.). 1997 ; 275 (5308) : 1943-1947. |
| PMID 9072974 |
| PTEN: sometimes taking it off can be better than putting it on. |
| Myers MP, Tonks NK |
| American journal of human genetics. 1997 ; 61 (6) : 1234-1238. |
| PMID 9399917 |
| Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. |
| Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH, Tavtigian SV |
| Nature genetics. 1997 ; 15 (4) : 356-362. |
| PMID 9090379 |
| Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. |
| Marsh DJ, Coulon V, Lunetta KL, Rocca-Serra P, Dahia PL, Zheng Z, Liaw D, Caron S, Dubouˆ© B, Lin AY, Richardson AL, Bonnetblanc JM, Bressieux JM, Cabarrot-Moreau A, Chompret A, Demange L, Eeles RA, Yahanda AM, Fearon ER, Fricker JP, Gorlin RJ, Hodgson SV, Huson S, Lacombe D, Eng C |
| Human molecular genetics. 1998 ; 7 (3) : 507-515. |
| PMID 9467011 |
| The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. |
| Maehama T, Dixon JE |
| The Journal of biological chemistry. 1998 ; 273 (22) : 13375-13378. |
| PMID 9593664 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 07-1999 | Michel Longy |
| Citation |
| This paper should be referenced as such : |
| Longy M . PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten). Atlas Genet Cytogenet Oncol Haematol. July 1999 . URL : http://AtlasGeneticsOncology.org/Genes/PTENID158.html |
This paper is referenced by INIST as such : |
| http://documents.irevues.inist.fr/bitstream/2042/37528/1/07-1999-PTENID158.pdf [ Bibliographic record ] |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed May 1 13:12:05 CEST 2013 |
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