Premium
Evidence for presence of mismatch repair gene expression positive Lynch syndrome cases in India
Author(s) -
Bashyam Murali D.,
Kotapalli Viswakalyan,
Raman Ratheesh,
Chaudhary Ajay K.,
Yadav Brijesh K.,
Gowrishankar Swarnalata,
Uppin Shantveer G.,
Kongara Ravikanth,
Sastry Regulagadda A.,
Vamsy Mohana,
Patnaik Sujit,
Rao Satish,
Dsouza Shoba,
Desai Devendra,
Tester Ashavaid
Publication year - 2015
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22244
Subject(s) - microsatellite instability , msh6 , msh2 , pms2 , biology , lynch syndrome , dna mismatch repair , mlh1 , genetics , multiplex ligation dependent probe amplification , germline mutation , gene duplication , gene , mutation , microsatellite , cancer research , microbiology and biotechnology , dna repair , exon , allele
Lynch syndrome (LS), the most common form of familial CRC predisposition that causes tumor onset at a young age, is characterized by the presence of microsatellite instability (MSI) in tumors due to germline inactivation of mismatch repair (MMR) system. Two MMR genes namely MLH1 and MSH2 account for majority of LS cases while MSH6 and PMS2 may account for a minor proportion. In order to identify MMR genes causing LS in India, we analyzed MSI and determined expression status of the four MMR genes in forty eight suspected LS patient colorectal tumor samples. Though a majority exhibited MSI, only 58% exhibited loss of MMR expression, a significantly low proportion compared to reports from other populations. PCR‐DNA sequencing and MLPA‐based mutation and exonic deletion/duplication screening respectively, revealed genetic lesions in samples with and without MMR gene expression. Interestingly, tumor samples with and without MMR expression exhibited significant differences with respect to histological (mucin content) and molecular (instability exhibited by mononucleotide microsatellites) features. The study has revealed for the first time a significant proportion of LS tumors not exhibiting loss of MMR expression. © 2014 Wiley Periodicals, Inc.