Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations

Brooke R. Druliner, Panwen Wang, Taejeong Bae, Saurabh Baheti, Seth Slettedahl, Douglas Mahoney, Nikolaos Vasmatzis, Hang Xu, Minsoo Kim, Matthew Bockol, Daniel O'Brien, Diane Grill, Nathaniel Warner, Miguel Munoz-Gomez, Kimberlee Kossick, Ruth Johnson, Mohamad Mouchli, Donna Felmlee-Devine, Jill Washechek-Aletto, Thomas Christopher SmyrkAnn L Oberg, Junwen Wang, Nicholas D Chia, Alexej Abyzov, David Ahlquist, Lisa Allyn Boardman

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Abstract

The majority of colorectal cancer (CRC) arises from precursor lesions known as polyps. The molecular determinants that distinguish benign from malignant polyps remain unclear. To molecularly characterize polyps, we utilized Cancer Adjacent Polyp (CAP) and Cancer Free Polyp (CFP) patients. CAPs had tissues from the residual polyp of origin and contiguous cancer; CFPs had polyp tissues matched to CAPs based on polyp size, histology and dysplasia. To determine whether molecular features distinguish CAPs and CFPs, we conducted Whole Genome Sequencing, RNA-seq, and RRBS on over 90 tissues from 31 patients. CAPs had significantly more mutations, altered expression and hypermethylation compared to CFPs. APC was significantly mutated in both polyp groups, but mutations in TP53, FBXW7, PIK3CA, KIAA1804 and SMAD2 were exclusive to CAPs. We found significant expression changes between CAPs and CFPs in GREM1, IGF2, CTGF, and PLAU, and both expression and methylation alterations in FES and HES1. Integrative analyses revealed 124 genes with alterations in at least two platforms, and ERBB3 and E2F8 showed aberrations specific to CAPs across all platforms. These findings provide a resource of molecular distinctions between polyps with and without cancer, which have the potential to enhance the diagnosis, risk assessment and management of polyps.

Original languageEnglish (US)
Article number3161
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Druliner, B. R., Wang, P., Bae, T., Baheti, S., Slettedahl, S., Mahoney, D., Vasmatzis, N., Xu, H., Kim, M., Bockol, M., O'Brien, D., Grill, D., Warner, N., Munoz-Gomez, M., Kossick, K., Johnson, R., Mouchli, M., Felmlee-Devine, D., Washechek-Aletto, J., ... Boardman, L. A. (2018). Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations. Scientific Reports, 8(1), [3161]. https://doi.org/10.1038/s41598-018-21525-4