Uncommon variants detected via hereditary cancer panel and suggestions for genetic counseling

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2023-07-01 DOI:10.1016/j.mrfmmm.2023.111831

Zeynep Özdemir , Ezgi Çevik , Ömür Berna Çakmak Öksüzoğlu , Mutlu Doğan , Öztürk Ateş , Ece Esin , İrem Bilgetekin , Umut Demirci , Çağlar Köseoğlu , Alper Topal , Nuri Karadurmuş , Haktan Bağış Erdem , Taha Bahsi

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引用次数: 0

Abstract

Objective

Hereditary cancer syndromes constitute 5–10% of all cancers. The development of next-generation sequencing technologies has made it possible to examine many hereditary cancer syndrome-causing genes in a single panel. This study's goal was to describe the prevalence and the variant spectrum using NGS in individuals who were thought to have a hereditary predisposition for cancer.

Material and method

Analysis was performed for 1254 who were thought to have a familial predisposition for cancer. We excluded 46 patients who were carrying BRCA1/2 variants in this study, for focusing on the rare gene mutations. Sequencing was performed using the Sophia Hereditary Cancer Solution v1.1 Panel and the Qiagen Large Hereditary Cancer Panel. The Illumina MiSeq system was used for the sequencing procedure. The software used for the data analyses was Sophia DDM and QIAGEN Clinical Insight (QCITM) Analyze. The resulting genomic changes were classified according to the current guidelines of ACMG/AMP.

Results

Pathogenic/likely pathogenic variants were detected in 172 (13.7%) of 1254 patients. After excluding the 46 BRCA1/2-positive patients, among the remaining 126 patients; there were 60 (4.8%) breast cancer, 33 (2.6%) colorectal cancer, 9 (0.7%) ovarian cancer, 5 (0.4%) endometrium cancer, 5 (0.4%) stomach cancer, 3 (0.2%) prostate cancer patients. The most altered genes were MUTYH in 27 (2.1%) patients, MMR genes (MLH1, MSH6, MSH, MSH2, PMS2 and EPCAM) in 26 (2%) patients, and ATM in 25 (2%) patients. We also examined the genotype-phenotype correlation in rare variants. Additionally, we identified 11 novel variations.

Conclusion

This study provided significant information regarding rare variants observed in the Turkish population because it was carried out with a large patient group. Personalized treatment options and genetic counseling for the patients are therefore made facilitated.

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通过遗传性癌症小组检测到的罕见变异和遗传咨询建议

遗传性癌症综合征占所有癌症的5-10%。下一代测序技术的发展使得在单个面板中检测许多遗传性癌症综合征引起基因成为可能。这项研究的目的是描述在被认为具有癌症遗传易感性的个体中使用NGS的患病率和变异谱。材料与方法对1254例被认为具有癌症家族易感性的患者进行分析。在这项研究中，我们排除了46名携带BRCA1/2变体的患者，因为我们关注的是罕见的基因突变。使用Sophia遗传性癌症解决方案v1.1面板和Qiagen大型遗传性癌症面板进行测序。Illumina MiSeq系统用于测序程序。用于数据分析的软件是Sophia DDM和QIAGEN Clinical Insight（QCITM）Analyze。根据ACMG/AMP的现行指南对由此产生的基因组变化进行分类。结果在1254名患者中检测到172例（13.7%）的致病性/可能的致病性变异。在排除46名BRCA1/2阳性患者后，在剩下的126名患者中；癌症60例（4.8%），癌症33例（2.6%），癌症9例（0.7%），癌症5例（0.4%），癌症5例（0.4%），癌症3例（0.2%）。改变最多的基因是27名（2.1%）患者的MUTYH，26名（2%）患者的MMR基因（MLH1、MSH6、MSH、MSH2、PMS2和EPCAM），25名（2%的）患者的ATM。我们还检测了罕见变异的基因型-表型相关性。此外，我们还发现了11种新的变体。结论这项研究提供了关于在土耳其人群中观察到的罕见变异的重要信息，因为它是在一个大的患者群体中进行的。因此，为患者提供了个性化的治疗选择和基因咨询。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 生物-毒理学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

51 days

期刊介绍： Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs. MR publishes articles in the following areas: Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence. The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance. Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing. Landscape of somatic mutations and epimutations in cancer and aging. Role of de novo mutations in human disease and aging; mutations in population genomics. Interactions between mutations and epimutations. The role of epimutations in chromatin structure and function. Mitochondrial DNA mutations and their consequences in terms of human disease and aging. Novel ways to generate mutations and epimutations in cell lines and animal models.