An Unusual Genomic Variant of Pancreatic Ductal Adenocarcinoma with an Indolent Clinical Course

We describe a patient with biopsy-proven locally advanced pancreatic
ductal adenocarcinoma (PDA) who underwent a modified course of
gemcitabine and stereotactic body radiation therapy. Whole exome
sequencing of this patient's 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. KRAS,
CDKN2A, TP53 or SMAD4. An analysis of germline DNA revealed no pathogenic
variants of significance. Whole exome and whole genome sequencing
identified a somatic mutation of RNF213 and an inversion/deletion of
CTNNA2 as the genetic basis of this 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.EGA study EGAS00001002192