title: Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas.
abstract: The AKT2 gene is one of the human homologues of v-akt, the transduced oncogene of the AKT8 virus, which induces lymphomas in mice. In previous studies, AKT2, 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 AKT2 alterations in ovarian and breast cancer. Southern-blot analysis demonstrated AKT2 amplification in 16 of 132 (12.1%) ovarian carcinomas and in 3 of 106 (2.8%) breast carcinomas. No AKT2 alteration was detected in 24 benign or borderline tumors. Northern-blot analysis revealed overexpression of AKT2 in 3 of 25 fresh ovarian carcinomas which were negative for AKT2 amplification. The difference in the incidence of AKT2 alterations in ovarian and breast cancer suggests a specific role for this gene in ovarian oncogenesis. No significant association was found between AKT2 amplification and amplification of the proto-oncogenes MYC and ERBB2, suggesting that amplification of AKT2 defines an independent subset of breast and ovarian cancers. Ovarian cancer patients with AKT2 alterations appear to have a poor prognosis. Amplification of AKT2 was especially frequent in undifferentiated tumors (4 of 8, p = 0.019), suggesting that AKT2 alterations may be associated with tumor aggressiveness.
authors.affiliation: Institute of Medical Genetics, Catholic University Medical School, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bellacosa
authors.forename: D
authors.initials: D
authors.lastname: de Feo
authors.forename: A K
authors.initials: AK
authors.lastname: Godwin
authors.forename: D W
authors.initials: DW
authors.lastname: Bell
authors.forename: J Q
authors.initials: JQ
authors.lastname: Cheng
authors.forename: D A
authors.initials: DA
authors.lastname: Altomare
authors.forename: M
authors.initials: M
authors.lastname: Wan
authors.forename: L
authors.initials: L
authors.lastname: Dubeau
authors.forename: G
authors.initials: G
authors.lastname: Scambia
authors.forename: V
authors.initials: V
authors.lastname: Masciullo
authors.forename: G
authors.initials: G
authors.lastname: Ferrandina
authors.forename: P
authors.initials: P
authors.lastname: Benedetti Panici
authors.forename: S
authors.initials: S
authors.lastname: Mancuso
authors.forename: G
authors.initials: G
authors.lastname: Neri
authors.forename: J R
authors.initials: JR
authors.lastname: Testa
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C494918:AKT1 protein, human; C494921:AKT2 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt