Whole-exome sequencing of pancreatic neoplasms with acinar differentiation

摘要: Pancreatic carcinomas with acinar differentiation, including cell carcinoma, pancreatoblastoma, and mixed are distinct pancreatic neoplasms poor prognosis. Although recent whole exome sequencing analyses have defined the somatic mutations that characterize other major of pancreas, molecular alterations underlying differentiation remain largely unknown. In current study, we sequenced exomes 23 surgically resected differentiation. These revealed a relatively large number genetic at both individual base pair chromosomal levels. There was an average 119 per carcinoma. When three outliers were excluded, there 64 tumor (range 12–189). The mean fractional allelic loss (FAL) 0.27 0–0.89) heterogeneity chromosome level confirmed in selected cases using fluorescent situ hybridization (FISH). No gene mutated >30% cancers. Genes altered pancreas occasionally targeted differentiation; SMAD4 six tumors (26%), TP53 (13%), GNAS two (9%), RNF43 one (4%) MEN1 (4%). Somatic identified genes which constitutional associated familial ductal adenocarcinoma, such as ATM, BRCA2, PALB2 (one each), well extra-pancreatic neoplasms, JAK1 four (17%) BRAF RB1 APC PTEN ARID1A MLL3 BAP1 Perhaps most importantly, found more than third these potentially targetable PALB2, BAP1, JAK1.