Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas

✍ Scribed by Alfonso Bellacosa; Daniela De Feo; Andrew K. Godwin; Daphne W. Bell; Jin Quan Cheng; Deborah A. Altomare; Minghong Wan; Louis Dubeau; Giovanni Scambia; Valeria Masciullo; Gabriella Ferrandina; Pierluigi Benedetti Panici; Salvatore Mancuso; Giovanni Neri; Joseph R. Testa

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: French
• Weight: 980 KB
• Volume: 64
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910640412

✦ Synopsis

The AKTZ gene is one of the human homologues of v-akt, the transduced oncogene of the AKTI virus, which induces lymphomas in mice. In previous studies, AKTZ, which codes for a serine-threonine protein kinase, was shown to be amplified and overexpressed in some human ovarian carcinoma cell lines and amplified in primary tumors of the ovary. To confirm and extend these findings, we conducted a large-scale, multicenter study of AKTZ alterations in ovarian and breast cancer. Southern-blot analysis demonstrated AKTZ amplification in I6 of I32 (I 2. I Yo) ovarian carcinomas and in 3 of 106 (2.8%) breast carcinomas.

No AKTZ alteration was detected in 24 benign or borderline tumors. Northem-blot analysis revealed overexpression of AKTZ in 3 of 25 fresh ovarian carcinomas which were negative for AKTZ amplification. The difference in the incidence of AKTZ alterations in ovarian and breast cancer suggests a specific role for this gene in ovarian oncogenesis. No significant association was found between AKTZ amplification and amplification of the proto-oncogenes MYC and ERBBZ, suggesting that amplification of AKTZ defines an independent subset of breast and ovarian cancers. Ovarian cancer patients with AKTZ alterations appear to have a poor prognosis. Amplification of AKTZ was especially frequent in undifferentiated tumors (4 of 8, p = 0.0 I9), suggesting that AKTZ alterations may be associated with tumor aggressiveness.