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Sci Rep. 2018 Feb 16;8(1):3161. doi: 10.1038/s41598-018-21525-4.

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

Author information

1
Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55905, USA.
2
Health Sciences Research, Mayo Clinic, Scottsdale, AZ, 85259, USA.
3
Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, 55905, USA.
4
Center for Genomic Sciences & School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
5
Information Technology, Mayo Clinic, Rochester, MN, 55905, USA.
6
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
7
Anatomic Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
8
Department of Health Sciences Research, Cancer Center Statistics Mayo Clinic, Rochester, MN, 55905, USA.
9
Department of Health Sciences Research, Center for Individualized Medicine, College of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
10
Department of Surgery, College of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
11
Department of Bioengineering and Physiology, College of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
12
Department of Health Sciences Research, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
13
Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55905, USA. boardman.lisa@mayo.edu.

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.

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