Array CGH Analysis Reveals Amplification of Met and AKT2 in Clear Cell Carcinoma of the Ovary
Yoriko Yamashita, Shinya Akatsuka, Yasushi Yatabe, Shinya Toyokuni. Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; Aichi Cancer Center, Nagoya, Aichi, Japan
Background: Clear cell carcinoma of the ovary (OCCC) is a chemo-resistant tumor with relatively worse prognosis and is frequently associated with endometriosis. Frequent mutations of the ARID1A gene and activating mutations of the PI3CA gene are reported in OCCC, but positive array CGH results for specific gene amplification have rarely been reported.
Design: In this study, we performed an array CGH analysis using formalin-fixed, paraffin-embedded samples from 13 OCCC patients to comprehensively evaluate gene copy number changes in OCCC samples. We also performed Taqman gene copy number analysis, fluorescence in situ hybridization, immunoblotting, and immunohistochemistry to confirm the array CGH results.
Results: Array CGH analysis revealed that Met gene amplification was present in 4 / 13 OCCC patients and 2 / 8 OCCC cell lines. Amplification of the AKT2 gene, which is a component of one of the downstream signaling pathway of Met together with PI3CA, was also detected in 3 / 13 OCCC patients and 2 / 8 OCCC cell lines. Totally 73 OCCC cases were examined by Taqman PCR for Met amplification, and 37.0% revealed to have Met gene amplification (>4 copies). Furthermore, stage 1 and 2 patients with Met gene amplification had significantly worse overall survival than patients without Met gene amplification (p=0.037).
Conclusions: We demonstrated for the first time Met and AKT2 amplification by array CGH in approximately half of the OCCC cases. Met amplification was significantly related to worse prognosis. Activation of the Met/PI3CA/AKT pathway may be one of the most important molecular events in OCCC carcinogenesis.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 151, Tuesday Afternoon