Hypermutation In Pancreatic Cancer

详细信息    查看全文

• 作者：Jeremy L. Humphris¹ ; ^&lowast ; ; Ann-Marie Patch² ; ³ ; ^&lowast ; ; Katia Nones² ; ³ ; Peter J. Bailey³ ; ⁴ ; Amber L. Johns¹ ; Skye McKay¹ ; David K. Chang⁴ ; ⁵ ; ⁶ ; ⁷ ; David K. Miller¹ ; ³ ; Marina Pajic¹ ; ⁸ ; Karin S. Kassahn³ ; ⁹ ; ¹⁰ ; Michael C.J. Quinn² ; ³ ; Timothy J.C. Bruxner³ ; Angelika N. Christ³ ; Ivon Harliwong³ ; Senel Idrisoglu³ ; Suzanne Manning³ ; Craig Nourse³ ; ⁸ ; Ehsan Nourbakhsh³ ; Andrew Stone¹ ; Peter J. Wilson³ ; Matthew Anderson³ ; J. Lynn Fink³ ; Oliver Holmes² ; ³ ; Stephen Kazakoff² ; ³ ; Conrad Leonard² ; ³ ; Felicity Newell² ; ³ ; Nick Waddell³ ; Scott Wood² ; ³ ; Ronald S. Mead¹ ; ¹¹ ; ¹² ; Qinying Xu² ; ³ ; Jianmin Wu¹ ; Mark Pinese¹ ; Mark J. Cowley¹ ; ⁸ ; Marc D. Jones¹ ; ⁴ ; Adnan M. Nagrial¹ ; Venessa T. Chin¹ ; Lorraine A. Chantrill¹ ; ¹³ ; Amanda Mawson¹ ; Angela Chou¹ ; ¹⁴ ; Christopher J. Scarlett¹ ; ¹⁵ ; Andreia V. Pinho¹ ; Ilse Rooman¹ ; Marc Giry-Laterriere¹ ; Jaswinder S. Samra¹⁶ ; ¹⁷ ; James G. Kench¹ ; ¹⁷ ; ¹⁸ ; Neil D. Merrett⁵ ; ¹⁹ ; Christopher W. Toon¹ ; Krishna Epari²⁰ ; Nam Q. Nguyen²¹ ; Andrew Barbour²²
• 关键词：Pancreatic Adenocarcinoma ; Sequencing ; Somatic Rearrangement ; Cancer Genetics
• 刊名：Gastroenterology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：152
• 期：1
• 页码：68-74.e2
• 全文大小：928 K
• 卷排序：152

文摘

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.