Evidence map›Paper›PMID 41433014›Full record

ArticleJournal of gastrointestinal cancer2025

Reduced Involvement of Major Mismatch Repair Genes in Sporadic Microsatellite Unstable Colorectal Cancer in an Indian Cohort.

Ashmala Naz, Sara A George, Shivani Yadav, Indra S Lama, Satish I Rao, Vijaya Tourani, Swarnalata Gowrishankar, Shantveer G Uppin, Murali D Bashyam

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Article in Journal of gastrointestinal cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Ashmala NazLaboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Inner Ring Road, Uppal, Hyderabad , 500039, Telangana, India.
Sara A George *Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Inner Ring Road, Uppal, Hyderabad , 500039, Telangana, India.
Shivani Yadav *Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Inner Ring Road, Uppal, Hyderabad , 500039, Telangana, India.
Indra S Lama *Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Inner Ring Road, Uppal, Hyderabad , 500039, Telangana, India.
Satish I RaoKrishna Institute of Medical Sciences, Hyderabad, Telangana, India.
Vijaya TouraniCARE Hospitals, Hyderabad, Telangana, India.
Swarnalata GowrishankarApollo Hospitals, Hyderabad, Telangana, India.
Shantveer G UppinNizam's Institute of Medical Sciences, Hyderabad, Telangana, India.
Murali D BashyamLaboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Inner Ring Road, Uppal, Hyderabad , 500039, Telangana, India. bashyam@cdfd.org.in.ORCID http://orcid.org/0000-0002-1967-5249

Funding

Department of Science and Technology, Ministry of Science and Technology, India EMR/2016/006192
6 · The paper itself

Abstract

purposeColorectal cancer (CRC) is the third leading cancer-type worldwide and is exhibiting an increasing incidence in developing countries including India. Aberrant activation of Wnt-signalling and Mismatch-Repair inactivation causing microsatellite instability are the two major CRC drivers. CpG island methylator phenotype, the third driver, exhibits extensive overlap with MSI. The mechanisms driving CRC in India are poorly understood. We attempted to characterize sporadic CRC caused by MSI and its complex interplay with other CRC drivers in patients from Telangana, India.

methodsTo determine the MSI status of our cohort, we analysed the instability statuses of five canonical microsatellites, expression statuses of major MMR genes, and the mutation statuses of the MLH1 and MSH2 genes. Detection of H3K36me3 was performed to assess for defects in MMR-complex recruitment. The methylation statuses of a panel of CIMP markers, in addition to the nuclear-stabilization statuses of β-catenin and p53 were also assessed to identify the involvement of other pathways.

resultsAmong 230 CRC patients, a majority of whom were males, ≥ 50 years old and harbouring late stage tumours in the rectum, low frequency of loss of major MMR genes was observed in MSI + tumors. MSH2 loss was detected in 16% of MSI + samples, a frequency significantly higher than previously reported. Causal genetic aberrations were undetected in 57% of MSI + tumors suggesting novel/non-canonical drivers.

conclusionsA majority of MSI + samples exhibited proficient expression of the four major MMR genes. The results highlight the importance of studying geographically-distinct populations to expand our understanding of CRC origins.

Indexed as

Colorectal NeoplasmsDNA Mismatch RepairMicrosatellite InstabilityAdultAgedCohort StudiesCpG IslandsDNA MethylationFemaleHumansIndiaMaleMiddle AgedMutationMutL Protein Homolog 1MutS Homolog 2 ProteinMLH1 protein, humanMSH2 protein, humanMutL Protein Homolog 1MutS Homolog 2 ProteinChromosomal instabilityColorectal cancerCpG island methylator phenotypeMicrosatellite instabilityMismatch repair

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.