Integrative proteomics reveals mitochondrial and immune signatures of MLH1 exon 13 deletion in Lynch syndrome-associated colorectal cancer.

ABSTRACT:

Background

Lynch syndrome is an inherited cancer predisposition caused by pathogenic variants in mismatch repair (MMR) genes. Large genomic rearrangements (LGRs) in MLH1 are often underestimated due to detection challenges. Functional analyses of specific variants such as MLH1 exon 13 deletion (MLH1-EX13 Del) remain scarce.

Methods

A three-generation Chinese family with Lynch syndrome was investigated. Targeted next-generation sequencing identified MLH1-EX13 Del in the proband, which was validated by qPCR in family members. Cancer patients underwent MMR immunohistochemistry (IHC) and microsatellite instability (MSI) testing. Data-independent acquisition proteomics was performed on four paired tumor and adjacent tissues, followed by Gene Ontology and KEGG enrichment analyses.

SUBMITTER: Chang C 

PROVIDER: S-EPMC12753366 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature