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

Juhari WKW 1 , Ahmad Amin Noordin KB 2 , Zakaria AD 3 , Rahman WFWA 4 , Mokhter WMMWM 3 , Hassan MRA 5 Show all authors , Sidek ASM 6 , Zilfalil BA 1

Affiliations 

  • 1 Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
  • 2 School of Dental Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
  • 3 Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
  • 4 Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
  • 5 Clinical Research Centre, Hospital Sultanah Bahiyah, Alor Star 05460, Kedah, Malaysia
  • 6 Surgery Department, Hospital Raja Perempuan Zainab II, Kota Bharu 15200, Kelantan, Malaysia
Genes (Basel), 2021 09 20;12(9).
PMID: 34573430 DOI: 10.3390/genes12091448

Abstract

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-IFNE, PTCH2 and SEMA3D-which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes-ANKDD1B, CENPM, CLDN5, MAGEB16, MAP3K14, MOB3C, MS4A12, MUC19, OR2L8, OR51Q1, OR51AR1, PDE4DIP, PKD1L3, PRIM2, PRM3, SEC22B, TPTE, USP29 and ZNF117-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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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