The pancreatic cancer genome revisited

被引：151

作者：

Hayashi, Akimasa ^{[1
,2
]}

Hong, Jungeui ^{[1
,3
]}

Iacobuzio-Donahue, Christine A. ^{[1
,3
,4
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, David M Rubenstein Ctr Pancreat Canc Res, Sloan Kettering Inst, 1275 York Ave, New York, NY 10021 USA

[2] Kyorin Univ, Sch Med, Dept Pathol, Tokyo, Japan

[3] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA

[4] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA

来源：

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY | 2021年 / 18卷 / 07期

关键词：

WNT RECEPTOR TURNOVER; MUTATIONAL SIGNATURES; SOMATIC MUTATIONS; DUCTAL ADENOCARCINOMA; GENE-MUTATIONS; DNA-DAMAGE; TUMOR; CELL; HETEROGENEITY; EVOLUTIONARY;

D O I：

10.1038/s41575-021-00463-z

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Pancreatic cancer is a genetic disease, and the recurrent genetic alterations characteristic of pancreatic cancer indicate the cellular processes that are targeted for malignant transformation. In addition to somatic alterations in the most common driver genes (KRAS, CDKN2A, TP53 and SMAD4), large-scale studies have revealed major roles for genetic alterations of the SWI/SNF and COMPASS complexes, copy number alterations in GATA6 and MYC that partially define phenotypes of pancreatic cancer, and the role(s) of polyploidy and chromothripsis as factors contributing to pancreatic cancer biology and progression. Germline variants that increase the risk of pancreatic cancer continue to be discovered along with a greater appreciation of the features of pancreatic cancers with mismatch repair deficiencies and homologous recombination deficiencies that confer sensitivity to therapeutic targeting. Wild-type KRAS pancreatic cancers, some of which are driven by alternative oncogenic events affecting NRG1 or NTRK1 - for which targeted therapies exist - further underscore that pancreatic cancer is formally entering the era of precision medicine. Given the vast developments within this field, here we review the wide-ranging and most current information related to pancreatic cancer genomics with the goal of integrating this information into a unifying description of the life history of pancreatic cancer. Vast developments are being made within the field of pancreatic cancer genomics. This Review discusses the wide-ranging and most current research with the goal of integrating this information into a unifying description of the life history of pancreatic cancer.

引用

页码：469 / 481

页数：13

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