Dataset Information

Somatic mutations in colorectal cancer are associated with the epigenetic modifications.

ABSTRACT: Colorectal cancer (CRC) mostly arises from progressive accumulation of somatic mutations within cells. Most commonly mutated genes like TP53, APC and KRAS can promote survival and proliferation of cancer cells. Although the molecular alterations and landscape of some specific mutations in CRC are well known, the presence of a somatic mutation signature related to genomic regions and epigenetic markers remain unclear. To find the signatures from a random distribution of somatic mutations in CRCs, we carried out enrichment analysis in different genomic regions and identified peaks of epigenetic markers. We validated that the mutation frequency in miRNA is dramatically higher than in flanking genomic regions. Moreover, we observed that somatic mutations in CRC and colon cancer cell lines are significantly enriched in CTCF binding sites. We also found these mutations are enriched for H3K27me3 in both normal sigmoid colon and colon cancer cell lines. Taken together, our findings suggest that there are some common somatic mutations signatures which provide new directions to study CRC.

SUBMITTER: Lei H

PROVIDER: S-EPMC7579689 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Somatic mutations in colorectal cancer are associated with the epigenetic modifications.

Lei Hongwei H Tao Kaixiong K

Journal of cellular and molecular medicine 20200831 20

Colorectal cancer (CRC) mostly arises from progressive accumulation of somatic mutations within cells. Most commonly mutated genes like TP53, APC and KRAS can promote survival and proliferation of cancer cells. Although the molecular alterations and landscape of some specific mutations in CRC are well known, the presence of a somatic mutation signature related to genomic regions and epigenetic markers remain unclear. To find the signatures from a random distribution of somatic mutations in CRCs, ...[more]

PMID: 32865336

Similar Datasets

Project description:BackgroundMutations in the POLE gene result in an ultra-hypermutated phenotype in colorectal cancer (CRC); however, the molecular characterisation of epigenetic alterations remains unclear. We examined the genetic and epigenetic profiles of POLE-mutant CRC to elucidate the clinicopathological features of the associated genetic and epigenetic alterations.ResultsTumour tissues (1,013) obtained from a cohort of patients with CRC were analysed to determine associations between the proofreading domain mutations of POLE with various clinicopathological variables, microsatellite instability (MSI) status, BRAF and KRAS mutations, and the methylation status of key regions of MLH1, MGMT, and SFRP2 promoters by calculating the methylation scores (range 0-6). Only four cases (0.4%) exhibited pathogenic POLE hotspot mutations (two p.P286R [c.857C > G], one p.V411L [c.1231G > C], and p.S459F [c.1376C > T] each), which were mutually exclusive to BRAF and KRAS mutations and MSI. CRC patients were divided into four subgroups: patients with POLE mutations (POLE, 0.4%, n = 4), patients with both MSI and extensive methylation in MLH1 (MSI-M, 2.9%, n = 29), patients with MSI but no extensive methylation in MLH1 (MSI-U, 3.6%, n = 36), and patients without MSI (non-MSI, 93.2%, n = 944). The POLE group was younger at diagnosis (median 52 years, P < 0.0001), with frequent right-sided tumour localisation (frequency of tumours located in the right colon was 100%, 93.1%, 36.1%, and 29.9% in POLE, MSI-M, MSI-U, and non-MSI, respectively; P < 0.0001), and was diagnosed at an earlier stage (frequency of stages I-II was 100%, 72.4%, 77.8%, and 46.6% in POLE, MSI-M, MSI-U, and non-MSI, respectively, P < 0.0001). The mean methylation score in POLE was not different from that in MSI-U and non-MSI, but the methylation signature was distinct from that of the other subgroups. Additionally, although the examined number of POLE-mutant tumours was small, the number of CD8-positive cells increased in tumours with partial methylation in the MLH1 gene.ConclusionsCRC patients with POLE proofreading mutations are rare. Such mutations are observed in younger individuals, and tumours are primarily located in the right colon. Diagnosis occurs at an earlier stage, and distinct epigenetic alterations may be associated with CD8 cell infiltration.

Dataset Information

Somatic mutations in colorectal cancer are associated with the epigenetic modifications.

Publications

Somatic mutations in colorectal cancer are associated with the epigenetic modifications.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets