Hypermutation In Pancreatic Cancer
Hypermutation In Pancreatic Cancer
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DOI：
10.1053/j.gastro.2016.09.060
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发表时间：
2017-01-01
期刊：
影响因子：
29.4
通讯作者：
Biankin, Andrew V.
中科院分区：
文献类型：
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作者：
Humphris, Jeremy L.;Patch, Ann-Marie;Biankin, Andrew V.
胰腺癌的分子多样性，有效的治疗方法很少。在其他几种癌症类型中，突变负担增加和DNA修复缺陷与对免疫检查点抑制剂的反应有关。我们询问了385个胰腺癌基因组，以确定超突变及其原因。推断DNA修复缺陷的突变特征在具有最高突变负荷的那些中富集。在1%的肿瘤中发现了错配修复缺陷，这些肿瘤具有MLH1和MSH2体细胞失活的不同机制。定义个体胰腺癌中的突变负荷和用于患者选择的最佳测定可以为胰腺癌免疫治疗的临床试验设计提供信息。
Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.