Cold Spring Harb Mol Case Stud 2017 Nov 21;3(6). Epub 2017 Nov 21.
Department of Pathology and Immunology, Washington University in St. Louis, Missouri 63130, USA.
is recurrently amplified in 5% of gastric cancers and 1%-4% of breast cancers; however, this molecular alteration has never been reported in a primary colorectal cancer specimen. Preclinical studies indicate that several FGFR tyrosine-kinase inhibitors (TKIs), such as AZD4547, have in vitro activity against the -amplified colorectal cell line, NCI-H716. The efficacy of these inhibitors is currently under investigation in clinical trials for breast and gastric cancer. Thus, better characterizing colorectal tumors for amplification could identify a subset of patients who may benefit from FGFR TKI therapies. Here, we describe a novel amplification identified by clinical next-generation sequencing in a primary colorectal cancer. Further characterization of the tumor by immunohistochemistry showed neuroendocrine differentiation, similar to the reported properties of the NCI-H716 cell line. These findings demonstrate that the spectrum of potentially clinically actionable mutations detected by targeted clinical sequencing panels is not limited to only single-nucleotide polymorphisms and insertions/deletions but also to copy-number alterations.