International Research Center (CIPE), A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília - UnB, Brasília, DF, Brazil.
Sci Rep. 2017 Jan 31;7:41677. doi: 10.1038/srep41677.
Patients with multiple primary cancers (MPCs) are suspected to have a hereditary cancer syndrome. However, only a small proportion may be explained by mutations in high-penetrance genes. We investigate two unrelated MPC patients that met Hereditary Breast and Ovaria Cancer criteria, both presenting triple negative breast tumors and no mutations in BRCA1, BRCA2 and TP53 genes. Germline rearrangements on chromosome 7q, involving over 40 Mb of the same region, were found in both patients: one with mosaic loss (80% of cells) and the other with cnLOH (copy-neutral loss of heterozygosity) secondary to maternal allele duplication. Five children tested had no alterations on 7q. The patients shared 330 genes in common on 7q22.1-q34, including several tumor suppressor genes (TSGs) previously related to breast cancer risk and imprinted genes. The analysis of the triple negative BC from one patient revealed a mosaic gain of 7q translated for over-expressed cancer-related genes. The involvement of TSGs and imprinted genes, mapped on 7q, has the potential of being associated to MPC risk, as well as cancer progression. To our knowledge, this is the first description of patients with MPCs that harbor constitutive large alterations on 7q.
患有多发性原发性癌症（MPC）的患者疑似患有遗传性癌症综合征。然而，只有一小部分可能是由高外显率基因突变引起的。我们研究了两名不相关的 MPC 患者，他们符合遗传性乳腺癌和卵巢癌标准，均表现为三阴性乳腺癌，且 BRCA1、BRCA2 和 TP53 基因均无突变。两名患者均存在染色体 7q 的种系重排，涉及同一区域超过 40Mb：一名患者存在镶嵌性缺失（80%的细胞），另一名患者存在母系等位基因重复导致的 cnLOH（杂合性丢失中性）。对 5 名子女的检测未发现 7q 上的改变。两名患者在 7q22.1-q34 上共有 330 个基因，包括几个先前与乳腺癌风险相关的肿瘤抑制基因（TSG）和印记基因。对一名患者的三阴性 BC 分析显示，7q 上存在过度表达的癌症相关基因的镶嵌性增益。位于 7q 上的 TSGs 和印记基因的参与，有可能与 MPC 风险以及癌症进展相关。据我们所知，这是首次描述患有 MPC 且存在 7q 上构成性大片段改变的患者。
