An unusual genomic variant of pancreatic ductal adenocarcinoma with an indolent clinical course.
An unusual genomic variant of pancreatic ductal adenocarcinoma with an indolent clinical course.
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DOI：
10.1101/mcs.a001701
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发表时间：
2017-07
影响因子：
1.8
通讯作者：
Iacobuzio-Donahue CA
中科院分区：
文献类型：
--
作者：
Kohutek ZA;Rosati LM;Hong J;Poling J;Attiyeh MA;Makohon-Moore A;Herman JM;Iacobuzio-Donahue CA
我们报告一位85岁德系犹太裔男性，经切片检查证实为局部晚期胰脏导管腺癌。患者接受了改良的吉西他滨和立体定向体部放射治疗，存活了42个月，胰头肿块稳定，在死于卒中并发症之前没有转移性疾病的证据。他的肿瘤的全外显子组测序揭示了一个简单的基因组景观，没有证据表明最常与PDA相关的基因中存在突变、拷贝数变化或结构改变（即，KRAS、CDKN 2A、TP 53或SMAD 4）。对他的生殖系DNA的分析显示没有显著的致病性变异。全外显子组和全基因组测序鉴定了RNF 213的体细胞突变和CTNNA 2的倒位/缺失作为他PDA的遗传基础。虽然PDA的典型特征是一组可预测的突变，但这些数据表明可能存在PDA的替代遗传路径，这可能与更惰性的临床过程相关。
We describe an 85-yr-old male of Ashkenazi Jewish descent with biopsy-proven locally advanced pancreatic ductal adenocarcinoma (PDA). The patient underwent a modified course of gemcitabine and stereotactic body radiation therapy and survived for 42 mo with a stable pancreatic head mass and no evidence of metastatic disease before death due to complications from a stroke. Whole-exome sequencing of his tumor revealed a simple genome landscape with no evidence of mutations, copy-number changes, or structural alterations in genes most commonly associated with PDA (i.e., KRAS, CDKN2A, TP53, or SMAD4). An analysis of his germline DNA revealed no pathogenic variants of significance. Whole-exome and whole-genome sequencing identified a somatic mutation of RNF213 and an inversion/deletion of CTNNA2 as the genetic basis of his PDA. Although PDA is classically characterized by a predictable set of mutations, these data suggest that alternate genetic paths to PDA may exist, which can be associated with a more indolent clinical course.