Hereditary pancreatic cancer has been attributed to variants of several cancer predisposition genes including ATM. While heterozygous pathogenic variants in the ATM gene are implicated as a cause of familial breast and pancreatic cancers to our knowledge ATM whole gene deletions have not been previously reported. We describe a contiguous gene deletion of the ATM locus in a multi-generation family of Italian descent with a strong family history of pancreatic cancer. A deletion of one copy of the entire ATM gene was identified by routine panel testing and further characterized by chromosomal microarray analysis. An 11q22.3 microdeletion of approximately 960 kb was identified that is predicted to result in loss of 10 genes including ATM. The deletion was identified in two additional family members including a presymptomatic daughter and an affected sibling. A normal disomic complement of the 11q22.3 region was detected in a third family member with a history of prostate and pancreatic cancer. Additional family members were not available for testing. Given available evidence that ATM haploinsufficiency can increase cancer risk, we predict that the observed copy number loss has likely contributed to hereditary cancer in this family. However, absence of the familial microdeletion in at least one affected family member suggests that ATM deletions are unlikely the sole contributing factor influencing tumor development in affected individuals. This case highlights 11q22.3 microdeletions of the ATM gene region as a possible risk factor for hereditary cancer, including pancreatic cancer. The same case provides a further cautionary tale for over interpretation of cancer risk associated tumor suppressor microdeletions and suggests that the variant may not be sufficient for tumor development or may modify the cancer risks associated with other, yet unidentified hereditary cancer genes.

遗传性胰腺癌已归因于包括ATM在内的几种癌症易感基因的变异。尽管据我们所知，ATM基因中的杂合致病变异是家族性乳腺癌和胰腺癌的病因，但据我们所知，ATM的全基因缺失以前尚未见报道。我们描述了意大利人血统的多代家族中具有强大胰腺癌家族史的ATM基因座的连续基因缺失。删除整个ATM的一份副本通过常规的面板检测鉴定了该基因，并通过染色体微阵列分析对其进行了进一步表征。鉴定出大约960 kb的11q22.3微缺失，预计会导致包括ATM在内的10个基因的丢失。在另外两个家庭成员中发现了这种缺失，包括一个有症状的女儿和一个受影响的兄弟姐妹。在有前列腺癌和胰腺癌病史的第三位家庭成员中检测到正常的11q22.3区二体补体。其他家庭成员无法进行测试。如果有可用的证据表明ATM单倍剂量不足会增加患癌症的风险，我们预测观察到的拷贝数减少可能是该家族遗传性癌症的原因。但是，至少一个受影响的家庭成员中没有家庭微缺失，这表明ATM缺失不太可能是影响受影响个体肿瘤发展的唯一因素。该病例强调了ATM基因区域的11q22.3微缺失是遗传性癌症（包括胰腺癌）的可能危险因素。