MS-MLPA reveals progressive age-dependent promoter methylation of tumor suppressor genes and possible role of IGSF4 gene in colorectal carcinogenesis of microsatellite instable tumors.
In 43 MSI-H colorectal cancers we searched for new targets of promoter methylation, inspected the nature of methylation process, and the influence of methylation at specific CpG site on gene expression. CpG methylation was detected in 12 tumor suppressor genes. Our findings suggest a potential role of IGSF4 gene in the development of colorectal tumors. According to the detected methylation pattern, two groups of tumors, significantly differing in age, exist in MSI-H colorectal cancers. Our study also suggests that methylation at a specific CpG island in the promoter could be the representative for gene silencing and therefore serve as a biomarker.
Berginc
Gasper
G
Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Bracko
Matej
M
Glavac
Damjan
D
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D053842:Microsatellite Instability; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins