Genekor Medical S.A, Athens, Greece.
Department of Pathology, IASSO General Hospital, Athens, Greece.
Mol Genet Genomic Med. 2020 Oct;8(10):e1242. doi: 10.1002/mgg3.1242. Epub 2020 Aug 27.
Carriers with pathogenic variants in MSH2 have increased risk to develop colorectal, endometrium, ovarian, and other types of cancer. The PALB2 is associated with breast, ovarian, pancreatic, and prostate cancer. We describe the case of a 42-year-old female diagnosed with endometrial cancer at the age of 42 years with a strong family history of colorectal cancer, which was referred to our private diagnostic laboratory for genetic testing.
In this study, we performed next-generation sequencing (NGS) using an amplicon based 26 genes panel. The presence of multi-exonic copy number variations (CNVs) was investigated by computational analysis and Multiplex Ligation-dependent Probe Amplification (MLPA).
A gross deletion of the genomic region encompassing exons 11-16 of the MSH2 and the loss-of-function variant c.757_758delCT, p.(Leu253Ilefs*3) in the PALB2 were identified in the proband.
Multigene analysis using NGS technology allows the identification of pathogenic variants in genes that would normally not be tested based on the patient diagnosis. In our case these results explained not only the personal and/or family history of cancer but also allowed the surveillance for prevention of other cancer types. Moreover, the detection of large genomic rearrangements should be routinely included in hereditary cancer testing.
携带 MSH2 致病突变的携带者患结直肠癌、子宫内膜癌、卵巢癌和其他类型癌症的风险增加。PALB2 与乳腺癌、卵巢癌、胰腺癌和前列腺癌有关。我们描述了一位 42 岁女性的病例，她在 42 岁时被诊断患有子宫内膜癌，家族中有结直肠癌病史，因此被转介到我们的私人诊断实验室进行基因检测。
在这项研究中，我们使用基于扩增子的 26 个基因 panel 进行了下一代测序（NGS）。通过计算分析和多重连接依赖性探针扩增（MLPA）调查了多外显子拷贝数变异（CNVs）的存在。
在该患者中发现 MSH2 外显子 11-16 基因组区域的大片段缺失以及 PALB2 中的功能丧失变异 c.757_758delCT，p.(Leu253Ilefs*3)。
使用 NGS 技术的多基因分析可鉴定通常不会根据患者诊断进行测试的基因中的致病突变。在我们的病例中，这些结果不仅解释了个人和/或家族的癌症史，还允许对其他类型的癌症进行监测和预防。此外，应常规将大的基因组重排检测纳入遗传性癌症检测中。
