Mutational spectra of PTEN/MMAC1 gene : A tumor suppressor with lipid phosphatase activity

• Published in: JNCI : Journal of the National Cancer Institute Vol. 91; no. 22; pp. 1922 - 1932
• Main Authors: IQBAL UNNISA ALI, SCHRIML, L. M, DEAN, M
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 17-11-1999; Oxford Publishing Limited (England)
• Subjects: Biological and medical sciences; Brain Neoplasms - genetics; Cancer; Carcinogenesis, carcinogens and anticarcinogens; DNA Mutational Analysis; endometrial carcinoma; Endometrial Neoplasms - genetics; Female; Frameshift Mutation; General aspects; Genes; Genes, Tumor Suppressor - genetics; Germ-Line Mutation; glioblastoma; Humans; Male; Medical sciences; Mutation; Neoplasms - enzymology; Neoplasms - genetics; Neoplasms - metabolism; Ovarian Neoplasms - genetics; phosphatase; Phosphatidylinositol Phosphates - metabolism; Phosphorylation; Prostatic Neoplasms - genetics; Protein-Serine-Threonine Kinases - metabolism; PTEN gene; Tumors; Adenocarcinoma; Carcinoma; Prostate disease; Phosphoric monoester hydrolases; Esterases; Carcinogenesis; Somatic mutation; Malignant glioma; Ovary; Uterine diseases; Familial cancer; Male genital diseases; Endometrium; Tumor suppressor gene; Human; Intracranial; Nervous system diseases; Urinary system disease; Enzyme; Malignant tumor; Gene expression; Female genital diseases; Cerebral disorder; Ovarian diseases; Germ line; Central nervous system disease; Hydrolases; Prostate; Bibliographic review
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/91.22.1922

PTEN/MMAC1 (phosphatase, tensin homologue/mutated in multiple advanced cancers) is a tumor suppressor protein that has sequence homology with dual-specificity phosphatases, which are capable of dephosphorylating both tyrosine phosphate and serine/threonine phosphate residues on proteins. The in vivo function of PTEN/MMAC1 appears to be dephosphorylation of phosphotidylinositol 3,4, 5-triphosphate. The PTEN/MMAC1 gene is mutated in the germline of patients with rare autosomal dominant cancer syndromes and in subsets of specific cancers. Here we review the mutational spectra of the PTEN/MMAC1 gene in tumors from various tissues, especially endometrium, brain, prostate, and ovary, in which the gene is inactivated very frequently. Germline and somatic mutations in the PTEN/MMAC1 gene occur mostly in the protein coding region and involve the phosphatase domain and poly(A)(6) stretches. Compared with germline alterations found in the PTEN/MMAC1 gene, there is a substantially increased frequency of frameshift mutations in tumors. Glioblastomas and endometrial carcinomas appear to have distinct mutational spectra, probably reflecting differences in the underlying mechanisms of inactivation of the PTEN/MMAC1 gene in the two tissue types. Also, depending on the tissue type, the gene appears to be involved in the initiation or the progression of cancers. Further understanding of PTEN/MMAC1 gene mutations in different tumors and the physiologic consequences of these mutations is likely to open up new therapeutic opportunities for targeting this critical gene.