Microarray comparative genomic hybridization을 이용한 진행된 장액성 난소암의 염색체 변화 분석

Abstract

Objective : Ovarian cancer is the leading cause of death in women with gynecological malignancies. The purpose of this study was to search characteristic genetic changes in advanced serous ovarian carcinomas using microarray comparative genomic hybridization (mCGH) and to identify genomic alterations specific to chemoresistant disease.

Methods : Genetic changes of 17 primary ovarian tumors were analyzed by MACArray(TM)-Karyo 4 K BAC-chip. All the patients had stage IIIc serous ovarian cancer optimally debulked and were initially treated with 6 cycles of platinum-based combination chemotherapy. Ten patients who progressed within 12 months from initial chemotherapy were defined as chemoresistant disease (control group), whereas 7 patients who did not recur for more than 36 months were defined as chemosensitive disease (studygroup).

Results : In control group, the mean number of clones with gain and loss was 288 (7.2%) and 508 (12.7%), respectively. In study group, the mean number of clones with gain and loss was 450 (11.3%) and 860 (21.5%), respectively. In study group, loss of DNA copy number was more frequent than gain (p=0.007). The chromosomal regions with gain of DNA copy numbers in more than 70% of each group were 1p36.33, 3q26.2, 8q24.3, 10q26.3, 12p11.21, 20q13.33, and 21q22.3, while the regions with loss of DNA copy number were 4p12, 5q13.2, 7q11.21, 8p23.1, 14q32.33, Xq13.3-Xq21.1, and Xq21.31. The more frequent chromosomal gains in study group were on 5p15.33 and 14q11.2, while the loss were on 4q34.2, 4q35.2, 5q15, 8p21.1, 8p21.2, 11p15.5, 13q14.13, 13q14.2, 13q32.1, 13q34, 16q22.2, 17p11.2, 17p12, and 22q12.3.

Conclusion : In this mCGH analysis, common chromosomal abnormalities specific to serous ovarian carcinoma were identified. This study suggests that several genomic aberrations might be related to chemoresistant phenotype in patients with advanced serous ovarian cancer.