Little is known about the molecular basis of aberrant protein glycosylation, a complex enzymatic process that is a hallmark of many human cancers including colorectal cancers (CRC), and how it may contribute to tumour progression.

In a new study published in Scientific Reports, scientists at Case Western Reserve University School of Medicine have successfully characterised the mutational landscapes of glycosylation-associated genes in colon cancer, identifying three glycosyltransferases as significant mutational targets in CRC.

These findings are significant as they strongly suggest that functionally deleterious mutations in glycosyltransferase genes in part underlie aberrant glycosylation, and contribute to the pathogenesis of molecular subsets of colon and other gastrointestinal malignancies.

Kishore Guda, DVM, PhD, assistant professor of general medical sciences (oncology) at the School of Medicine, led this critical research, involving the targeted re-sequencing of 430 glycosylation-associated genes and matched primary tumour tissues.

Through this process, Guda and his team identified three glycosyltransferases (B3GNT2, B4GALT2, ST6GALNAC2) as significant mutational targets in CRCs.

Analysis of independent large-scale tumour tissue datasets confirmed recurrent mutations within these genes in colon and other gastrointestinal cancers.

The study lays important groundwork for the future characterisation of these glycosyltransferases that may provide additional insights into the biologic role of these genes in colon cancer progression.

"With so many questions surrounding the potential role of aberrant glycosylation in tumour progression, we were excited to conduct this research that builds on our previous findings of mutations in the gene encoding for the enzyme GALNT12 in a subset of colon cancer cases," said Dr Guda.

"Our findings demonstrate that these mutant glycosyltransferases have a significant impact on the encoded enzymatic activity and/or the migratory potential of colon carcinoma cells, and set up future research that can further explore their role in tumour progression."

Source: Case Western Reserve University