Genetic alterations in ovarian carcinoma: with specific reference to histological subtypes.
Multiple genetic changes including activation of proto-oncogenes and inactivation of tumor suppressor gene are involved in the development of human ovarian cancer. We describe such genetic alterations with specific reference to histological subtypes. K-ras activation is specific for mucinous tumors including adenomas. Borderline tumors and carcinomas, suggesting that K-ras activation may be associated with the mucinous differentiation rather than malignant transformation. Inactivation of p53 is detected in 30-40% of ovarian carcinoma. Mutations are more frequently observed in serous carcinomas, but not found in adenomas or rarely found in borderline tumors, suggesting that p53 mutations may be directly involved in malignant transformation. TGFbeta-2 mutations are found in 50% of endometrioid carcinoma, but rarely in other type. Loss of DCC mRNA expression is found in 50% of serous carcinomas but less frequently in other type. Loss of DCC expression is rare in borderline tumors and adenomas, suggesting that inactivation of DCC may be directly involved in malignant transformation. Microsatellite instability (MI) is found in 17% of ovarian carcinomas, and is frequently found in endometrioid carcinomas. Although inactivation of p16 by point mutation or deletion is rare, p16 inactivation by loss of expression is relatively common.
Fujita
Masami
M
Department of Obstetrics and Gynecology, Osaka Rosai Hospital, Osaka, Japan.
Enomoto
Takayuki
T
Murata
Yuji
Y
D017766:Acid Anhydride Hydrolases; D005260:Female; D016163:Genes, DCC; D019942:Genes, p16; D016158:Genes, p53; D011905:Genes, ras; D042822:Genomic Instability; D006801:Humans; D018895:Microsatellite Repeats; D009363:Neoplasm Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; D000099170:Bis(5'-adenosyl)triphosphatase