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

Autor:	Juhari WKW; Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia.; Malaysian Node of the Human Variome Project, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia., Ahmad Amin Noordin KB; School of Dental Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia., Zakaria AD; Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia., Rahman WFWA; Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia., Mokhter WMMWM; Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia., Hassan MRA; Clinical Research Centre, Hospital Sultanah Bahiyah, Alor Star 05460, Kedah, Malaysia., Sidek ASM; Surgery Department, Hospital Raja Perempuan Zainab II, Kota Bharu 15200, Kelantan, Malaysia., Zilfalil BA; Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia.; Malaysian Node of the Human Variome Project, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia.
Jazyk:	angličtina
Zdroj:	Genes [Genes (Basel)] 2021 Sep 20; Vol. 12 (9). Date of Electronic Publication: 2021 Sep 20.
DOI:	10.3390/genes12091448
Abstrakt:	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.
Databáze:	MEDLINE
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