Frequent inactivating germline mutations in DNA repair genes in patients with Ewing sarcoma
Frequent inactivating germline mutations in DNA repair genes in patients with Ewing sarcoma
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DOI：
10.1038/gim.2016.206
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发表时间：
2017-08-01
影响因子：
8.8
通讯作者：
Khan, Javed
中科院分区：
文献类型：
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作者：
Brohl, Andrew S.;Patidar, Rajesh;Khan, Javed
目的：尤文肉瘤是一种高度恶性的小圆形蓝细胞肿瘤，主要发生在青少年和年轻成人人群。长期以来，人们一直怀疑这种癌症的遗传易感性存在，但这种疾病的生殖系遗传基础还没有得到很好的established.Methods：我们进行了全基因组或全外显子组测序的样本从175例尤文sarcoma.Results：我们发现致病性或可能致病的生殖系突变在我们的队列的13.1%。致病性突变是高度富集的基因参与DNA损伤修复和癌症易感性syndrome.Conclusion相关基因：我们的研究结果报道在这里有重要的临床意义尤文肉瘤患者和家庭的影响。应考虑为受这种疾病影响的患者和家庭提供遗传咨询，以利用现有的风险管理策略。我们的研究还强调了生殖细胞测序对参加精确医学方案的患者的重要性。
Purpose: Ewing sarcoma is a small round blue cell tumor that is highly malignant and predominantly affects the adolescent and young adult population. It has long been suspected that a genetic predisposition exists for this cancer, but the germ-line genetic underpinnings of this disease have not been well established.Methods: We performed germline variant analysis of whole-genome or whole-exome sequencing of samples from 175 patients affected by Ewing sarcoma.Results: We discovered pathogenic or likely pathogenic germline mutations in 13.1% of our cohort. Pathogenic mutations were highly enriched for genes involved with DNA damage repair and for genes associated with cancer predisposition syndromes.Conclusion: Our findings reported here have important clinical implications for patients and families affected by Ewing sarcoma. Genetic counseling should be considered for patients and families affected by this disease to take advantage of existing risk management strategies. Our study also highlights the importance of germline sequencing for patients enrolled in precision-medicine protocols.