Next-generation sequencing (NGS)-based cancer risk screening with multigene panels has become the most successful method for programming cancer prevention strategies. ATM germ-line heterozygosity has been described to increase tumor susceptibility. In particular, families carrying heterozygous germ-line variants of ATM gene have a 5- to 9-fold risk of developing breast cancer. Recent studies identified ATM as the second most mutated gene after CHEK2 in BRCA-negative patients. Nowadays, more than 170 missense variants and several truncating mutations have been identified in ATM gene. Here, we present the molecular characterization of a new ATM deletion, identified thanks to the CNV algorithm implemented in the NGS analysis pipeline. An automated workflow implementing the SOPHiA Genetics' Hereditary Cancer Solution (HCS) protocol was used to generate NGS libraries that were sequenced on Illumina MiSeq Platform. NGS data analysis allowed us to identify a new inactivating deletion of exons 19-27 of ATM gene. The deletion was characterized both at the DNA and RNA level.

中文翻译：

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与遗传性乳腺癌相关的新 ATM 缺失的特征

使用多基因面板进行基于下一代测序 (NGS) 的癌症风险筛查已成为制定癌症预防策略的最成功方法。ATM 种系杂合性已被描述为增加肿瘤易感性。特别是，携带 ATM 基因杂合种系变异的家庭患乳腺癌的风险是 5 到 9 倍。最近的研究确定 ATM 是 BRCA 阴性患者中仅次于 CHEK2 的第二大突变基因。目前，已在 ATM 基因中鉴定出 170 多个错义变异和几个截短突变。在这里，我们展示了新 ATM 缺失的分子特征，这要归功于在 NGS 分析管道中实施的 CNV 算法。实施 SOPHiA Genetics 的自动化工作流程 遗传性癌症解决方案 (HCS) 协议用于生成在 Illumina MiSeq 平台上测序的 NGS 文库。NGS 数据分析使我们能够识别出 ATM 基因外显子 19-27 的新失活缺失。缺失在 DNA 和 RNA 水平上都有特征。