Genomic landscape of pancreatic cancer in the Japanese version of the Cancer Genome Atlas

Abstract

Abstract Background Pancreatic cancer (PC) is one of the most aggressive cancers worldwide. Although many studies have investigated genomic alterations, the genomic landscape of Japanese PC patients has not been fully elucidated. Methods We used whole‐exome sequencing, cancer gene panel deep‐sequencing, and microarray gene expression profiling data derived from the Japanese version of the Cancer Genome Atlas (JCGA) in 93 PC cases. Results Somatic driver mutations were identified in 65.6% of samples in 19 genes. The median tumor mutation burden (TMB) value was 0.24 Muts/Mb (interquartile range, 0.15–0.64 Muts/Mb). The commonly mutated genes were KRAS (58%), TP53 (40%), CDKN2A (10%), SMAD4 (10%), FGFR2 (9%), and PKHD1 (9%). Frequent germline variation genes were BRCA1 (8%), CDH1 (5%), MET (5%), MSH6 (5%), and TEK (5%). Frequent chromosomal arm alterations included copy number gains in 2q (42%), 7q (24%), and 3q (24%), and copy number losses in 19p (62%), 19q (47%), 12q (34%), and 7q (30%). A prognostic analysis according to the presence of driver mutations showed that overall survival (OS) in the driver mutation‐positive group was significantly worse in comparison to that of the driver mutation‐negative group (median, 23.1 vs 46.7 mo; P = .010). A Cox proportional hazards analysis for OS identified driver mutation (hazard ratio [HR], 1.89; P = .025) and lymph node metastasis (HR, 3.27; P = .002) as independent prognostic factors. Conclusion The present results from the JCGA dataset constitute a fundamental resource for genomic medicine for PC patients, especially in Japan.

Keywords

• copy number variant
• driver mutation
• pancreatic cancer
• prognosis