Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Breast Cancer Res Treat. 2010 Dec;124(3):857-61. doi: 10.1007/s10549-010-1095-5. Epub 2010 Aug 10.
It has been reported that one biallelic missense mutation in the RAD51C gene was found in a Fanconi anemia-like disorder and six monoallelic pathogenic mutations were identified in 480 BRCA1/2 negative breast and ovarian cancer pedigrees but not in 620 pedigrees with breast cancer only. Additionally, the RAD51C gene was reported to be involved in gene fusion events in the MCF-7 breast cancer cell line. We performed complete sequencing and fusion gene breakpoint screening to detect deleterious mutations and chromosomal structure change in the RAD51C gene. Ninety-two hereditary gynecological cancer patients with a family history of breast and ovarian cancer but not carrying BRCA1/2 mutations were studied. In addition, 46 breast cancer cell lines were screened for the gene fusion events. Ten DNA sequence variants but no deleterious mutations were identified. We did not observe the occurrence of the known gene fusion either. We were unable to confirm the contribution of the RAD51C gene to hereditary breast and ovarian cancer (HBOC) in this relatively small cohort. Nonetheless, larger studies in diverse populations to fully investigate the mutation spectrum of the RAD51C gene are needed.
据报道,在类似于范可尼贫血症的疾病中发现 RAD51C 基因的两个等位基因突变,在 480 个 BRCA1/2 阴性的乳腺癌和卵巢癌家系中鉴定出 6 个单等位基因致病性突变,但在 620 个仅乳腺癌家系中未发现。此外,RAD51C 基因被报道参与 MCF-7 乳腺癌细胞系中的基因融合事件。我们进行了完整的测序和融合基因断点筛查,以检测 RAD51C 基因中的有害突变和染色体结构变化。研究了 92 名遗传性妇科癌症患者,这些患者有乳腺癌和卵巢癌的家族史,但不携带 BRCA1/2 突变。此外,还筛选了 46 种乳腺癌细胞系中的基因融合事件。鉴定出 10 个 DNA 序列变异,但没有发现有害突变。我们也没有观察到已知的基因融合的发生。在这个相对较小的队列中,我们无法确认 RAD51C 基因对遗传性乳腺癌和卵巢癌(HBOC)的贡献。尽管如此,仍需要在不同人群中进行更大规模的研究,以充分调查 RAD51C 基因的突变谱。