Cancer Research Laboratory, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Eur J Cancer. 2012 Feb;48(3):305-10. doi: 10.1016/j.ejca.2011.11.008. Epub 2011 Nov 29.
Tetraploidy and aneuploidy can be caused by cell division errors and are frequently observed in many human carcinomas. We have recently reported delayed cytokinesis in primary human fibroblasts from BRCA2 mutation carriers, implying a function for the BRCA2 tumour suppressor in completion of cell division. Here, we address ploidy aberrations in breast tumours derived from BRCA2 germline mutation carriers. Ploidy aberrations were evaluated from flow cytometry histograms on selected breast tumour samples (n=236), previously screened for local BRCA mutations. The ploidy between BRCA2-mutated (n=71) and matched sporadic (n=165) cancers was compared. Differences in ploidy distribution were examined with respect to molecular tumour subtypes, previously defined by immunohistochemistry on tissue microarray sections. Tetraploidy was significantly 3 times more common in BRCA2 breast cancers than sporadic. However, no differences were found in the overall ploidy distribution between BRCA2-mutation carriers and non-carriers. In BRCA2 cancers, tetraploidy was associated with luminal characteristics. The increased frequency of tetraploidy in BRCA2 associated cancers may be linked to cell division errors, particularly cytokinesis. Additionally, tetraploidy emerges predominantly in BRCA2 breast cancers displaying luminal rather than triple-negative phenotypes.
四倍体和非整倍体可由细胞分裂错误引起，在许多人类癌中经常观察到。我们最近报道了 BRCA2 突变携带者原代人成纤维细胞的胞质分裂延迟，这暗示 BRCA2 肿瘤抑制因子在完成细胞分裂中具有功能。在这里，我们研究了源自 BRCA2 种系突变携带者的乳腺肿瘤中的倍性异常。从先前针对局部 BRCA 突变筛选的选定乳腺肿瘤样本（n=236）的流式细胞术直方图评估倍性异常。比较了 BRCA2 突变（n=71）和匹配的散发性（n=165）癌症之间的倍性差异。通过组织微阵列切片上的免疫组织化学，针对分子肿瘤亚型检查了倍性分布的差异。BRCA2 乳腺癌中的四倍体明显比散发性乳腺癌多 3 倍。但是，在 BRCA2 突变携带者和非携带者之间，整体倍性分布没有差异。在 BRCA2 癌症中，四倍体与腔特征相关。BRCA2 相关癌症中四倍体的增加频率可能与细胞分裂错误有关，特别是胞质分裂。此外，四倍体主要出现在显示腔特征而非三阴性表型的 BRCA2 乳腺癌中。
