A germline MBD4 mutation was identified in a patient with colorectal oligopolyposis and early ‑onset cancer: A case report.

A germline MBD4 mutation was identified in a patient with colorectal oligopolyposis and early‑onset cancer: A case report. Oncol Rep. 2019 Jul 17;: Authors: Tanakaya K, Kumamoto K, Tada Y, Eguchi H, Ishibashi K, Idani H, Tachikawa T, Akagi K, Okazaki Y, Ishida H Abstract A 42‑year‑old woman presented with ~30 adenomatous polyps of the left sided‑colon with early rectosigmoid cancer. The patient had no previous medical history and no familial history of inherited colorectal disease. No germline gene mutations associated with colorectal adenomatous polyposis, including APC regulator of WNT signaling pathway, mutY DNA glycosylase, DNA polymerase‑ε, catalytic subunit, DNA polymerase δ1, catalytic subunit, and mismatch repair genes, were detected via germline genetic testing. A heterozygous germline mutation in methyl‑CpG binding domain 4, DNA glycosylase (MBD4), c.217C>T/p.Gln73*, which resulted in the generation of a stop codon, was identified by genetic analyses including whole‑exome sequencing. Immunohistochemical staining analysis revealed that the expression of MBD4 protein was absent in the cancer tissue, while it was expressed in the normal epithelium. Sequencing and copy‑number analyses demonstrated the loss of the remaining allele of MBD4 in the cancer tissue. Furthermore, somatic mutation signature analysis showed preferential transition of cytosine to thymine residues at CpG dinucleotides in cancer tissues...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

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Conclusions The current review reports recent epidemiological and experimental data supporting the bright future of dietary polyphenols as chemopreventive, anti-inflammatory, immunomodulatory, and anticancer agents in CRC (Figure 1). The polyphenol-rich diet not only may represent a chemopreventive treatment but also has important function on immune system by promoting symbiont and commensal bacterial populations, increases reciprocal interaction between host and microbiota which in turn have important effects on immune function Evidence underlines the use of polyphenols as sensitizers of chemo/radiotherapies paving the w...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Authors: Matos P, Jordan P Abstract The subgroup of colon cancer (CRC) characterized by mutation in the BRAF gene and high mutation rate in the genomic DNA sequence, known as the microsatellite instability (MSI) phenotype, accounts for roughly 10% of the patients and derives from polyps with a serrated morphology. In this review, both features are discussed with regard to therapeutic opportunities. The most prevalent cancer-associated BRAF mutation is BRAF V600E that causes constitutive activation of the pro-proliferative MAPK pathway. Unfortunately, the available BRAF-specific inhibitors had little clinical benefi...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Abstract Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a CpG island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potentials. Detecting serrated lesions, including SSA/Ps with and without dysplasia/carcinoma, is critical, but SSA/Ps can be difficult to detect, are inconsistently identified by endoscopists a...
Source: World Journal of Gastroenterology - Category: Gastroenterology Authors: Tags: World J Gastroenterol Source Type: research
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Source: Molecular Carcinogenesis - Category: Molecular Biology Authors: Tags: RESEARCH ARTICLE Source Type: research
ConclusionSquamous cell carcinomas have been described in Lynch syndrome and Muir-Torre syndrome in two studies and two case reports. This new case further supports a possible relationship between Lynch syndrome and squamous cell carcinoma.
Source: Hereditary Cancer in Clinical Practice - Category: Cancer & Oncology Source Type: research
Conclusions: The theoretical merits of the low-dose carcinogenesis hypothesis are well founded with clear biological relevance, and therefore, the premise warrants further investigation. Expert recommendations include the need for better insights into the ways in which noncarcinogenic constituents might combine to uniquely affect the process of cellular transformation (in vitro) and environmental carcinogenesis (in vivo), including investigations of the role of key defense mechanisms in maintaining transformed cells in a dormant state. The scientific community will need to acknowledge limitations of animal-based models in ...
Source: EHP Research - Category: Environmental Health Authors: Tags: Reviews February 2017 Source Type: research
Over last 15 years it has been recognized that a significant proportion of colorectal cancers arise from serrated polyps, previously called hyperplastic polyps that were thought to be of no malignant potential. Minimum estimates of the proportion are based on the presence of the BRAFV600E mutation since this only occurs in serrated polyps. In a series of cancers occurring between 1998 and 2007 13% had a BRAFV600E mutation whereas this proportion was 20% in our recent series from 2012 to 2013 (1). The proportion may be increasing since serrated pathway cancers are predominantly proximal and the rate of decline in incidence ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Understanding the Origins of Colorectal Neoplasia Source Type: research
Familial adenomatous polyposis (FAP) is the most common high-penetrant Mendelian syndrome predisposing to adenomatous polyposis. FAP is caused by monoallelic germline mutations in the gene APC, and shows autosomal dominant inheritance. A somatic mutation in the remaining wild type APC allele results in loss of APC activity, which is one of the initiating events of adenoma development. The high proliferation rate in the colorectum increases the chance that an intestinal epithelium cell obtains this somatic second hit, which explains why FAP patients usually develop hundreds to thousands of adenomatous polyps and, if untreat...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: High-Risk Cohorts and Genetic Susceptibility Source Type: research
Introduction: In the last 20 years, advances in our understanding of the molecular genetics and epigenetics of colorectal cancer (CRC) have led to the discovery and assessment of a large number of cancer specific molecular alterations as biomarkers for CRC. The majority of these biomarkers have not evolved into clinical assays for a variety of reasons, but a small number of them are currently in use in the clinic and a larger number of emerging biomarkers are under active investigation for their use in early detection, prognosis and prediction for treatment response.Early detection assays: 1. Stool-based biomarkers: Since ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Molecular Diagnostics Source Type: research
Objective Sessile serrated adenomas (SSAs) are the precursors of at least 15% of colorectal carcinomas, but their biology is incompletely understood. We performed a clinicopathological and molecular analysis of a large number of the rarely observed SSAs with dysplasia/carcinoma to better define their features and the pathways by which they progress to carcinoma. Design A cross-sectional analysis of 137 SSAs containing regions of dysplasia/carcinoma prospectively collected at a community GI pathology practice was conducted. Samples were examined for BRAF and KRAS mutations, the CpG island methylator phenotype (CIMP) and im...
Source: Gut - Category: Gastroenterology Authors: Tags: Colon cancer Source Type: research
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