Stratification of patients with colorectal cancer without the recorded family history

Abstract

Colorectal cancer (CRC) is a multifactorial disease and one of the most malignant tumours. In addition to the sporadic form, familial occurrences, particularly hereditary non-polyposis CRC-Lynch syndrome (LS)-are often observed. LS is caused by a germline mutation in mismatch repair (MMR) genes, whose task it is to correct errors in the DNA structure that result from its replication. The aim of the present study was to stratify CRC patients using molecular diagnostics and next generation sequencing, according to the chosen criteria [positive for microsatellite instability (MSI) and negative for a BRAF mutation and MutL homolog 1 ( MLH1 ) methylation], and subsequently to detect pathological germline mutations in MMR genes in Slovak patients. To exclude patients with MSI from further testing, the present study detected the BRAF V600E mutation and examined MLH1 methylation status. From the 300 CRC patients, 37 cases with MSI were identified. In the MSI-positive samples, 13 cases of BRAF V600E mutation were recorded. In 24 BRAF -negative patients, 11 cases of epigenetic methylation of MLH1 and 12 cases without MLH1 methylation suspected for LS were detected, and it was not possible to analyse the methylation phenotype of 1 sample. Thus, the present study reports the novel deletion of four nucleotides, 1627_1630del AAAG (Glu544Lysfs*26) in MSH6 , probably associated with LS. A second case with a nonsense mutation in MSH was also detected, namely MMR_c.1030C>T (p.Q344X).

Repurposing non‑invasive prenatal testing data: Population study of single nucleotide variants associated with colorectal cancer and Lynch syndrome

“…We have performed a literature search in PubMed focused on population studies of CRC and LS in Slovakia from 2010–2020 using next-generation sequencing. In the Slovak population, only a few population studies of risk variants have been conducted to elucidate the etiology of CRC ( 55 – 57 ). In general, little is known about risk variants associated with CRC or LS in the Slovak population.…”

Repurposing Non-invasive prenatal testing data; population study of single nucleotide variants associated with colorectal cancer and Lynch syndrome

“…We have performed a literature search in PubMed focused on population studies of CRC and LS in Slovakia from 2010-2020 using next-generation sequencing. In the Slovak population, only a few population studies of risk variants have been conducted to elucidate the etiology of CRC (Kašubová et al 2019;Mahmood et al 2014;Skerenova et al 2017). In general, little is known about risk variants associated with CRC or LS in the Slovak population.…”

Breast Cancer in Young Women: Status Quo and Advanced Disease Management by a Predictive, Preventive, and Personalized Approach

“…Histopathological, molecular, genetic, and genomic studies have demonstrated that young women with BC show an increased rate of more aggressive subtypes with an overall worse prognosis, increased genetic susceptibility, differential tumor gene expression, specific genomic signatures, as well as alternations in epigenetic events including miRNA expression in comparison with postmenopausal women with BC [46]. Advances in novel technologies such as next-generation sequencing (NGS) and gene microarray have resulted in enormous progression and deluge sequence data about gene polymorphisms or determination of patterns of gene expression implicated in various pathological states [47,48,49,50]. Rummel et al [50] enrolled female patients within the Clinical Breast Cancer Project between 2001 and 2015 that were diagnosed with invasive BC before the age of 40.…”