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

  • Shadi Javan Department of Immunology, Isfahan Medical School, Isfahan University of Medical Sciences, Isfahan, Iran.
  • Alireza Andalib Department of Immunology, Isfahan Medical School, Isfahan University of Medical Sciences, Isfahan, Iran.
  • Ali Hosseini Bereshneh Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
  • Mohammad Hassan Emami Department of Internal Medicine, Isfahan Medical School, Isfahan University of Medical Sciences, Isfahan, Iran.
  • Rasul Salehi Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
  • Fatemeh Karami Mail Department of Medical Genetics, Applied Biophotonics Research Center, Sciences and Research Branch, Islamic Azad University, Tehran, Iran.
Hereditary nonpolyposis colorectal cancer, MSH2, MLH1, CEA, PCR-SSCP


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 MSH2 and exon 15 of MLH1 gene through polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). Positive PCR results were further analyzed through exon sequencing. Serum CEA level was determined using the ELISA test. PCR-SSCP was positive in 8 out of 18 patients (44%) for exons 7 of MSH2 gene, 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.


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How to Cite
Javan S, Andalib A, Hosseini Bereshneh A, Emami M, Salehi R, Karami F. Frequent Novel Variations Within MSH2 and MLH1 Genes in a Subset of Iranian Families With Hereditary Non-Polyposis Colorectal Cancer. Acta Med Iran. 57(3):147-151.