An unusual genomic variant of pancreatic ductal adenocarcinoma with an indolent clinical course

• Published in: Cold Spring Harbor molecular case studies Vol. 3; no. 4; p. a001701
• Main Authors: Kohutek, Zachary A, Rosati, Lauren M, Hong, Junguei, Poling, Justin, Attiyeh, Marc A, Makohon-Moore, Alvin, Herman, Joseph M, Iacobuzio-Donahue, Christine A
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.07.2017
• Subjects: Adenocarcinoma - genetics; Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Aged, 80 and over; alpha Catenin - genetics; alpha Catenin - metabolism; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - genetics; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Exome; Exome Sequencing; Gemcitabine; Genomics; Humans; INDEL Mutation - genetics; Mutation; Pancreas - metabolism; Pancreatic Neoplasms; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - genetics; Research Report; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; pancreatic adenocarcinoma; neoplasm of the pancreas
• ISSN: 2373-2865; 2373-2873
• DOI: 10.1101/mcs.a001701

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., , or ). An analysis of his germline DNA revealed no pathogenic variants of significance. Whole-exome and whole-genome sequencing identified a somatic mutation of and an inversion/deletion of 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.