Vietri Maria Teresa, Caliendo Gemma, Casamassimi Amelia, Cioffi Michele, De Paola Maria Laura, Napoli Claudio, Molinari Anna Maria
Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, I-80138 Naples, Italy.
Oncol Rep. 2015 Mar;33(3):1243-7. doi: 10.3892/or.2014.3685. Epub 2014 Dec 22.
Male breast cancer (MBC) is a rare disease, accounting for ~1% of all breast cancer cases worldwide. Although other genes are also involved, predisposing genetic factors to MBC include germline mutations in the BRCA genes (BRCA2). Among the other genes, partner and localizer of BRCA2 (PALB2) is considered a moderate-penetrance breast cancer susceptibility gene that may also play a role in MBC predisposition. Thus, the aim of the present study was to determine the PALB2 gene status in 8 MBC cases selected from a cohort of 181 hereditary breast and/or ovarian cancer probands. We performed PALB2 mutational analysis by direct sequencing of 13 exons and adjacent intronic regions. This study showed the presence of a PALB2 truncating mutation in 1/8 (12.5%) cases. This novel mutation was named c.1285_1286delAinsTC (p.I429SfsX12) and is localized in exon 4 of PALB2, in the region encoding for the ChAM motif which is important for the efficient association of PALB2 to chromatin and for recruitment of the BRCA complex to accumulate RAD51 at double-strand break sites. Our findings indicate that PALB2 could be added to the list of breast cancer susceptibility genes also in families with MBC cases.
男性乳腺癌（MBC）是一种罕见疾病，占全球所有乳腺癌病例的约1%。尽管其他基因也参与其中，但MBC的遗传易感因素包括BRCA基因（BRCA2）的种系突变。在其他基因中，BRCA2的伴侣和定位蛋白（PALB2）被认为是一种中度 penetrance 的乳腺癌易感基因，也可能在MBC易感性中起作用。因此，本研究的目的是确定从181名遗传性乳腺癌和/或卵巢癌先证者队列中选取的8例MBC病例的PALB2基因状态。我们通过对13个外显子和相邻内含子区域进行直接测序来进行PALB2突变分析。本研究显示在1/8（12.5%）的病例中存在PALB2截短突变。这种新突变被命名为c.1285_1286delAinsTC（p.I429SfsX12），位于PALB2的第4外显子，在编码ChAM基序的区域，该基序对于PALB2与染色质的有效结合以及BRCA复合物在双链断裂位点募集RAD51以积累至关重要。我们的研究结果表明，在患有MBC病例的家族中，PALB2也可被添加到乳腺癌易感基因列表中。
