Application of Next Generation Sequencing Approach to
Molecular Diagnosis Of Hereditary Colorectal Cancer:
Identification Of A Novel Heterozygous Single Nucleotide
Germline Deletion In Msh2 Gene Cause Lynch Syndrome?
Volume 3 - Issue 5
Zhe Lu1†, Lewei Yang2†, Santasree Banerjee3, Meifang Xiao1* and Yan Zhang4*
1Hainan Women and Children’s Medical Center, China
2Department of Radiation Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, China
3Department of Genetics, College of Basic Medical Sciences, Jilin University, China
4Department of Pathology, Shenzhen Longhua District Maternity & Child Healthcare Hospital, China
Yan Zhang, Department of Pathology, Shenzhen Longhua District Maternity & Child Healthcare Hospital,
Meifang Xiao, Clinical Laboratory, Maternal and Child Health Hospital of Hainan Province, Haikou, China
Germline mutations in DNA mismatch repair (MMR) genes including MSH2, MLH1, MSH6 and PMS2 causes Lynch syndrome
(LS). Lynch syndrome (LS) is the autosomal dominantly inherited familial form of colorectal cancer (CRC) predisposing syndrome.
In our present study, we identified and screen a five generation Chinese family with LS. According to the Amsterdam II criteria,
clinical diagnosis has been done for the affected members of this family. In this study, we performed genetic molecular study for 79
members (11 patients and 68 unaffected members) of this five generation Chinese family and 100 normal healthy control individuals
of same ethnic background. Targeted next generation sequencing and Sanger sequencing identified a novel heterozygous single
nucleotide germline deletion (c.1427delC) in MSH2 gene in the proband, which is co-segregated well with the disease phenotype
among all the affected family members. This novel heterozygous deletion (c.1427delC) in MSH2 gene leads to the formation of a
premature stop codon (p.Pro476Leufs*6) which finally results into the formation of a truncated MSH2 protein. Our present finding
expands the mutation spectrum for the MSH2 gene as well as establishes the significance of targeted next generation sequencing
for identifying novel candidate mutations for patients with Lynch syndrome.
Keywords: Lynch Syndrome; MSH2 Gene; Targeted Next Generation Sequencing; Novel Mutation; DNA Mismatch Repair Gene.