Whole-Genome Profiles of Malay Colorectal Cancer Patients with Intact MMR Proteins.

BACKGROUND

This study aimed to identify new genes associated with CRC in patients with normal mismatch repair (MMR) protein expression.

METHOD

Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms.

RESULTS

An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes- and -which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes- and -harbouring nonsense variants were prioritised. These genes are suggested to play a role in cancer predisposition and to be associated with cancer risk. Pathway enrichment analysis indicated significant enrichment in the olfactory signalling pathway.

CONCLUSION

This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients.