Centre for Cancer Genomics and Predictive Medicine, Melbourne, Victoria, Australia.
Clin Cancer Res. 2011 Dec 1;17(23):7273-82. doi: 10.1158/1078-0432.CCR-11-2080. Epub 2011 Oct 5.
Serous ovarian carcinomas are the predominant epithelial ovarian cancer subtype and it has been widely believed that some or all of these may arise from precursors derived from the ovarian surface epithelium or fimbriae, although direct molecular evidence for this is limited. This study aimed to conduct copy number (CN) analysis using a series of benign and borderline serous ovarian tumors to identify underlying genomic changes that may be indicative of early events in tumorigenesis.
High resolution CN analysis was conducted on DNA from the epithelial and fibroblast components of a cohort of benign (N = 39) and borderline (N = 24) serous tumors using the Affymetrix OncoScan assay and SNP6.0 arrays.
CN aberrations were detected in the epithelium of only 2.9% (1 of 35) of serous cystadenomas and cystadenofibromas. In contrast, CN aberrations were detected in the epithelium of 67% (16 of 24) of the serous borderline tumors (SBT). Unexpectedly, CN aberrations were detected in the fibroblasts of 33% (13 of 39) of the benign serous tumors and in 15% (3 of 20) of the SBTs. Of the 16 cases with CN aberrations in the fibroblasts, 12 of these carried a gain of chromosome 12.
Chromosome 12 trisomy has been previously identified in pure fibromas, supporting the concept that a significant proportion of benign serous tumors are in fact primary fibromas with an associated cystic mass. This is the first high resolution genomic analysis of benign serous ovarian tumors and has shown not only that the majority of benign serous tumors have no genetic evidence of epithelial neoplasia but that a significant proportion may be more accurately classified as primary fibromas.
浆液性卵巢癌是最主要的上皮性卵巢癌亚型，人们普遍认为，这些肿瘤中的一些或全部可能源自卵巢表面上皮或输卵管的前体细胞，尽管直接的分子证据有限。本研究旨在对一系列良性和交界性浆液性卵巢肿瘤进行拷贝数（CN）分析，以确定可能预示肿瘤发生早期事件的潜在基因组变化。
利用 Affymetrix OncoScan 检测和 SNP6.0 阵列对一组良性（n=39）和交界性（n=24）浆液性肿瘤的上皮和纤维母细胞成分的 DNA 进行高分辨率 CN 分析。
仅在 2.9%（35 例中的 1 例）浆液性囊腺瘤和囊纤维瘤的上皮中检测到 CN 异常。相比之下，在 67%（24 例中的 16 例）交界性浆液性肿瘤（SBT）的上皮中检测到 CN 异常。出乎意料的是，在 33%（39 例中的 13 例）良性浆液性肿瘤和 15%（20 例中的 3 例）SBT 的纤维母细胞中检测到 CN 异常。在纤维母细胞中存在 CN 异常的 16 例病例中，有 12 例存在 12 号染色体三体。
此前在纯纤维瘤中已鉴定出 12 号染色体三体，这支持了一个观点，即相当一部分良性浆液性肿瘤实际上是具有相关囊性肿块的原发性纤维瘤。这是对良性浆液性卵巢肿瘤的首次高分辨率基因组分析，不仅表明大多数良性浆液性肿瘤没有上皮性肿瘤的遗传证据，而且相当一部分可能更准确地归类为原发性纤维瘤。
