title: Gene Signature in Sessile Serrated Polyps Identifies Colon Cancer Subtype.
abstract: Sessile serrated colon adenoma/polyps (SSA/P) are found during routine screening colonoscopy and may account for 20% to 30% of colon cancers. However, differentiating SSA/Ps from hyperplastic polyps (HP) with little risk of cancer is challenging and complementary molecular markers are needed. In addition, the molecular mechanisms of colon cancer development from SSA/Ps are poorly understood. RNA sequencing (RNA-Seq) was performed on 21 SSA/Ps, 10 HPs, 10 adenomas, 21 uninvolved colon, and 20 control colon specimens. Differential expression and leave-one-out cross-validation methods were used to define a unique gene signature of SSA/Ps. Our SSA/P gene signature was evaluated in colon cancer RNA-Seq data from The Cancer Genome Atlas (TCGA) to identify a subtype of colon cancers that may develop from SSA/Ps. A total of 1,422 differentially expressed genes were found in SSA/Ps relative to controls. Serrated polyposis syndrome (n = 12) and sporadic SSA/Ps (n = 9) exhibited almost complete (96%) gene overlap. A 51-gene panel in SSA/P showed similar expression in a subset of TCGA colon cancers with high microsatellite instability. A smaller 7-gene panel showed high sensitivity and specificity in identifying BRAF-mutant, CpG island methylator phenotype high, and MLH1-silenced colon cancers. We describe a unique gene signature in SSA/Ps that identifies a subset of colon cancers likely to develop through the serrated pathway. These gene panels may be utilized for improved differentiation of SSA/Ps from HPs and provide insights into novel molecular pathways altered in colon cancer arising from the serrated pathway. Cancer Prev Res; 9(6); 456-65. ©2016 AACR.
authors.affiliation: Department of Gastroenterology, University of Utah, Salt Lake City, Utah. priyanka.kanth@hsc.utah.edu.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Kanth
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, Utah. Huntsman Cancer Institute, Salt Lake City, Utah.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Bronner
authors.affiliation: Huntsman Cancer Institute, Salt Lake City, Utah. Division of Epidemiology, University of Utah, Salt Lake City, Utah.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Boucher
authors.affiliation: Department of Gastroenterology, University of Utah, Salt Lake City, Utah. Huntsman Cancer Institute, Salt Lake City, Utah.
authors.forename: Randall W
authors.initials: RW
authors.lastname: Burt
authors.affiliation: Division of Genetic Epidemiology, University of Utah, Salt Lake City, Utah.
authors.forename: Deborah W
authors.initials: DW
authors.lastname: Neklason
authors.affiliation: Department of Gastroenterology, University of Utah, Salt Lake City, Utah. The Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Curt H
authors.initials: CH
authors.lastname: Hagedorn
authors.affiliation: Department of Gastroenterology, University of Utah, Salt Lake City, Utah.
authors.forename: Don A
authors.initials: DA
authors.lastname: Delker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003110:Colonic Neoplasms / Q000235:genetics*; D003111:Colonic Polyps / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D059467:Transcriptome; D055815:Young Adult