Microarray comparative genomic hybridization을 이용한 진행된 장액성 난소암의 염색체 변화 분석 = Microarray Comparative Genomic Hybridization Analysis of Chromosomal Changes in Advanced Serous Ovarian Carcinoma

다국어 초록 (Multilingual 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™-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 (study group).
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.

국문 초록 (Abstract)

목 적: 진행된 장액성 난소암에서 특징적인 염색체의 변화를 microarray comparative genomic hybridization (mCGH) 을 이용하여 알아보고 항암제 저항성 난소암에서 특징적인 염색체 변화가 무엇인지 알아보고자 하였다.
방 법: 성공적인 일차 종양감축술 (optimal cytoreductive surgery) 후 platinum을 기초로 한 복합항암화학요법을 시행 받은 장액성 난소암 병기 IIIc인 환자를 대상으로 하였다. 총 17명의 난소암 환자의 암 조직에서 DNA를 추출하여 MACArray™-Karyo 4 K BAC-chip을 이용하여 염색체의 변화를 분석하였다. 항암제 투여 시작 후 36개월 이상 재발하지 않은 7명의 환자를 항암제 감수성 난소암(대조군)으로 분류하였고 항암제 투여 시작 후 12개월 이내에 병이 진행된 10명의 환자를 항암제 저항성 난소암(시험군)으로 분류하였다.
결 과: 4000개의 BAC clone중 대조군에서 증가를 보인 clone의 수는 평균288개 (7.2%)이었고 감소를 보인 clone의 수는 평균 508개 (12.7%)이었다. 시험군에서는 증가를 보인 clone의 수는 평균450개 (11.3%)이었고 감소를 보인 clone의 수는 평균 860개 (21.5%)이었다(P=0.007). 대조군과 시험군에 공통적으로 증가되어 있는 염색체는 1p36.33, 3q26.2, 8q24.3, 10q26.3, 12p11.21, 20q13.33, 21q22.3 이었고 감소되어 있는 염색체는 4p12, 5q13.2, 7q11.21, 8p23.1, 14q32.33, Xq13.3-Xq21.1, Xq21.31이었다. 시험군에서만 통계적으로 유의하게 증가되어 있는 염색체는 5p15.33와 14q11.2이었고 감소되어 있는 염색체는 4q34.2, 4q35.2, 5q15, 8p21.1, 8p21.2, 11p15.5, 13q14.13, 13q14.2, 13q32.1, 13q34, 16q22.2, 17p11.2, 17p12, 22q12.3이었다.
결 론: 항암제 저항성 난소암의 mCGH 분석 결과 염색체 소실이 증가보다 더 많았고 그 중에 염색체 13q32.1과 8p21.1의 소실이 항암제 감수성 난소암보다 가장 유의하게 차이가 있는 것으로 나타났다. 난소암에서 염색체의 소실이 많을수록 항암제 저항성을 보일 가능성이 높을 것으로 판단된다. 그러나 이런 결과를 확인하기 위해서는 향 후 추가적인 연구가 더 필요하다고 사료된다.

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