Frequent Novel Variations Within MSH2 and MLH1 Genes in a Subset of Iranian Families With Hereditary Non-Polyposis Colorectal Cancer

Hereditary non-polyposis colorectal cancer (HNPCC) is the most frequent autosomal dominant predisposition for development of colorectal cancer (CRC) caused by germline defects in mismatch repair (MMR) genes. Current study was aimed to find genetic variations in MSH2 and MLH1 genes and their correlat...

Full description

Saved in:
Bibliographic Details
Published in:Acta medica Iranica 2019-05, Vol.57 (3), p.147-151
Main Authors: Javan, Shadi, Andalib, Alireza, Ali Hosseini Bereshneh, Mohammad Hassan Emami, Salehi, Rasul, Karami, Fatemeh
Format: Article
Language:eng ; fre
Subjects:
CEA
Colorectal cancer
Genes
Genetic disorders
Hereditary nonpolyposis colorectal cancer
MLH1
MSH2
Mutation
PCR-SSCP
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Hereditary non-polyposis colorectal cancer (HNPCC) is the most frequent autosomal dominant predisposition for development of colorectal cancer (CRC) caused by germline defects in mismatch repair (MMR) genes. Current study was aimed to find genetic variations in MSH2 and MLH1 genes and their correlation with the serum levels of Carcinoembryonic Antigen (CEA) in seven Iranian HNPCC families. Seven unrelated Iranian families including 11 HNPCC patients and 7 affected family members were selected. They were initially screened for mutations in exons 7 of MSH2and exon 15 ofMLH1 gene through polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP)Positive PCR results were further analyzed through exon sequencingSerum CEA level was determined using the ELISA test. PCR-SSCP was positive in 8 out of 18 patients (44%) for exons 7 of MSH2gene, whereas two samples (11%) demonstrated to bear a mutation in exon 15 of the MLH1 gene. Sequencing analysis of both amplified exons in positive and negative samples have confirmed no mutation in negative samples while revealed 5 and 7 novel mutations in exons 7 and 15, respectively. The mean serum concentration of CEA had a significant difference between HNPCC patients and their healthy family members. Our results demonstrated that the PCR-SSCP method has high specificity and sensitivity in the first step of mutation screening of HNPCC families. High frequency of novel alterations found in the current assay may revise the mutation screening of MSH2 and MLH1 genes and abet further assessment of their frequency among individual HNPCC patients.
ISSN:0044-6025
1735-9694
DOI:10.18502/acta.v57i3.1815