Mucinous adenocarcinoma of the colon and rectum: A genomic analysis

Abstract

Background and Objectives Mucinous adenocarcinoma is a distinct subtype of colorectal cancer (CRC) with a worse prognosis when compared with non‐mucinous adenocarcinoma. The aim of this study was to compare somatic mutations and copy number alteration (CNA) between mucinous and non‐mucinous CRC. Methods Data from The Cancer Genome Atlas‐colon adenocarcinoma and rectum adenocarcinoma projects were utilized. Mucinous and non‐mucinous CRC were compared with regard to microsatellite status, overall mutation rate, the most frequently mutated genes, mutations in genes coding for mismatch repair (MMR) proteins and genes coding for mucin glycoproteins. CNA analysis and pathway analysis was undertaken. Results Mucinous CRC was more likely to be microsatellite instability‐high (MSI‐H) and hypermutated. When corrected for microsatellite status the single‐nucleotide variation and insertion‐deletion rate was similar between the two cohorts. Mucinous adenocarcinoma was more likely to have mutations in genes coding for MMR proteins and mucin glycoproteins. Pathway analysis revealed further differences between the two histological subtypes in the cell cycle, RTK‐RAS, transforming growth factor‐β, and TP53 pathways. Conclusions Mucinous CRC has some distinct genomic aberrations when compared with non‐mucinous adenocarcinoma, many of which are driven by the increased frequency of MSI‐H tumors. These genomic aberrations may play an important part in the difference seen in response to treatment and prognosis in mucinous adenocarcinoma.

Investigating the utility of extended mutation analysis in gastrointestinal peritoneal metastasis

“…When small bowel tumors were excluded, restricting the analysis to the two most common peritoneal tumors (colon, appendix), a mutation burden of >1 remained associated with decreased survival. The detection of multiple mutations may be a potential surrogate for the level of cellular chaos yielding a more aggressive, refractory phenotype 31,32 . Currently, hotspot gene platforms are the most common panel, but further expansion of these panels combined with chromosomal and methylation analysis may help develop powerful and discriminatory tools for outcome and selection of best therapies 33,34 …”

“…However, the primary tumors were not available for testing in this study, and the omental implants were yielding a more aggressive, refractory phenotype. 31,32 Currently, hotspot gene platforms are the most common panel, but further expansion of these panels combined with chromosomal and methylation analysis may help develop powerful and discriminatory tools for outcome and selection of best therapies. 33,34 The association of TP53 and SMAD4 with poor survival was observed across all three high-grade tumor categories with peritoneal metastasis.…”

Identification of differentially expressed genes between mucinous adenocarcinoma and other adenocarcinoma of colorectal cancer using bioinformatics analysis

“…Previous studies have suggested that the genetic origin of mucinous colorectal adenocarcinoma is related to the BRAF, microsatellite instability (MSI), and CpG island methylation phenotype (CIMP) pathways. 7,8 There are differences in the expression of mucin family members in MC: MUC2 and MUC5 are highly expressed, whereas MUC1 shows low expression. The differential expression of mucin is related to the risk of metastasis and death.…”

Low-kilovolt x-ray intraoperative radiotherapy for pT3 locally advanced colon cancer: a single-institution retrospective analysis

“…Overall survival was poor especially for small-cell neuroendocrine carcinomas [25]. Comparing with non-mucinous adenocarcinoma, mucinous adenocarcinoma was a distinct subgroup of colon cancer with a worse prognosis [26]. Thus, instead of affecting our current results, it indicated that we achieved quite good results.…”