Abstract
BackgroundNasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition.MethodsA discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124).ResultsSix putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR) = 7.27; 95% CI = 2.96–17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75–10.11) overlapping MICA/HCP5/HCG26 genes.ConclusionOur results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.
Highlights
Nasopharyngeal carcinoma (NPC) (OMIM 161550 and 607107) is a malignant tumour arising in the nasopharyngeal mucosa
Six putative Copy number variant regions (CNVRs) overlapping GRM5, MHC Class I Polypeptide-Related Sequence A (MICA)/HLA complex 5 (HCP5)/HLA complex group 26 (HCG26), LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition
copy number variations (CNV) overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR
Summary
Nasopharyngeal carcinoma (NPC) (OMIM 161550 and 607107) is a malignant tumour arising in the nasopharyngeal mucosa. It is a rare malignancy in most parts of the world (ASR = 1 case per 100,000 per year), but a highly endemic disease in selected demographics such as Southern Chinese population of Guangdong (as high as 15 to 25 cases per 100,000 per year) [1], native Greenlanders [2] and migrants of the Southern Chinese in America, Australia, and Malaysia [3, 4]. Despite many reports linking SNP variants to NPC predisposition, structural variants such as CNVs and its possible influence on NPC predisposition remain grossly neglected. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition
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