title: Evidence for presence of mismatch repair gene expression positive Lynch syndrome cases in India.
abstract: 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.
authors.affiliation: Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
authors.forename: Murali D
authors.initials: MD
authors.lastname: Bashyam
authors.affiliation: Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
authors.forename: Viswakalyan
authors.initials: V
authors.lastname: Kotapalli
authors.affiliation: Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
authors.forename: Ratheesh
authors.initials: R
authors.lastname: Raman
authors.affiliation: Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Chaudhary
authors.affiliation: Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
authors.forename: Brijesh K
authors.initials: BK
authors.lastname: Yadav
authors.affiliation: Histopathology, Apollo Hospitals, Hyderabad, India.
authors.forename: Swarnalata
authors.initials: S
authors.lastname: Gowrishankar
authors.affiliation: Nizam's Institute of Medical Sciences, Hyderabad, India.
authors.forename: Shantveer G
authors.initials: SG
authors.lastname: Uppin
authors.affiliation: Nizam's Institute of Medical Sciences, Hyderabad, India.
authors.forename: Ravikanth
authors.initials: R
authors.lastname: Kongara
authors.affiliation: Nizam's Institute of Medical Sciences, Hyderabad, India.
authors.forename: Regulagadda A
authors.initials: RA
authors.lastname: Sastry
authors.affiliation: Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, India.
authors.forename: Mohana
authors.initials: M
authors.lastname: Vamsy
authors.affiliation: Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, India.
authors.forename: Sujit
authors.initials: S
authors.lastname: Patnaik
authors.affiliation: Krishna Institute of Medical Sciences, Hyderabad, India.
authors.forename: Satish
authors.initials: S
authors.lastname: Rao
authors.affiliation: Hinduja Hospital, Mumbai, India.
authors.forename: Shoba
authors.initials: S
authors.lastname: Dsouza
authors.affiliation: Hinduja Hospital, Mumbai, India.
authors.forename: Devendra
authors.initials: D
authors.lastname: Desai
authors.affiliation: Hinduja Hospital, Mumbai, India.
authors.forename: Ashavaid
authors.initials: A
authors.lastname: Tester
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics
keywords: MMR; MSI; exonic rearrangement; lynch syndrome; mutation