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: Priyanka Kanth, Mary P Bronner, Kenneth M Boucher, Randall W Burt, Deborah W Neklason, Curt H Hagedorn, Don A Delker
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 9 Issue 6 Pg. 456-65 (06 2016) ISSN: 1940-6215 [Electronic] United States
• PMID: 27026680 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2016 American Association for Cancer Research.

Topics

• Adolescent
• Adult
• Aged
• Colonic Neoplasms (genetics)
• Colonic Polyps (genetics)
• Female
• Humans
• Male
• Middle Aged
• Polymerase Chain Reaction
• Sensitivity and Specificity
• Transcriptome
• Young Adult