A genome wide study of copy number variation associated with nasopharyngeal carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci

Joyce Siew Yong Low, Yoon Ming Chin, Taisei Mushiroda, Michiaki Kubo, Gopala Krishnan Govindasamy, Kin Choo Pua, Yoke Yeow Yap, Lee Fah Yap, Selva Kumar Subramaniam, Cheng Ai Ong, Tee Yong Tan, Alan Soo Beng Khoo, Ching Ching Ng

Research output: Contribution to journalArticle

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Abstract

Background Nasopharyngeal 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. Methods A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina1 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). Results Six 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. Conclusion Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

Original languageEnglish
Article numbere0145774
JournalPloS one
Volume11
Issue number1
DOIs
Publication statusPublished - 05-01-2016

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carcinoma
Genes
Association reactions
Genome
Chromosomes
loci
genome
Assays
Linings
odds ratio
Odds Ratio
chromosomes
nasopharynx
Polymerase Chain Reaction
mica
neoplasms
Glandular and Epithelial Neoplasms
Nasopharynx
assays
Nasopharyngeal carcinoma

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Low, Joyce Siew Yong ; Chin, Yoon Ming ; Mushiroda, Taisei ; Kubo, Michiaki ; Govindasamy, Gopala Krishnan ; Pua, Kin Choo ; Yap, Yoke Yeow ; Yap, Lee Fah ; Subramaniam, Selva Kumar ; Ong, Cheng Ai ; Tan, Tee Yong ; Khoo, Alan Soo Beng ; Ng, Ching Ching. / A genome wide study of copy number variation associated with nasopharyngeal carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci. In: PloS one. 2016 ; Vol. 11, No. 1.
@article{ab8c7c44e76c49b9a55a65b7276f9fce,
title = "A genome wide study of copy number variation associated with nasopharyngeal carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci",
abstract = "Background Nasopharyngeal 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. Methods A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina1 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). Results Six 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. Conclusion Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.",
author = "Low, {Joyce Siew Yong} and Chin, {Yoon Ming} and Taisei Mushiroda and Michiaki Kubo and Govindasamy, {Gopala Krishnan} and Pua, {Kin Choo} and Yap, {Yoke Yeow} and Yap, {Lee Fah} and Subramaniam, {Selva Kumar} and Ong, {Cheng Ai} and Tan, {Tee Yong} and Khoo, {Alan Soo Beng} and Ng, {Ching Ching}",
year = "2016",
month = "1",
day = "5",
doi = "10.1371/journal.pone.0145774",
language = "English",
volume = "11",
journal = "PLoS One",
issn = "1932-6203",
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number = "1",

}

Low, JSY, Chin, YM, Mushiroda, T, Kubo, M, Govindasamy, GK, Pua, KC, Yap, YY, Yap, LF, Subramaniam, SK, Ong, CA, Tan, TY, Khoo, ASB & Ng, CC 2016, 'A genome wide study of copy number variation associated with nasopharyngeal carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci', PloS one, vol. 11, no. 1, e0145774. https://doi.org/10.1371/journal.pone.0145774

A genome wide study of copy number variation associated with nasopharyngeal carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci. / Low, Joyce Siew Yong; Chin, Yoon Ming; Mushiroda, Taisei; Kubo, Michiaki; Govindasamy, Gopala Krishnan; Pua, Kin Choo; Yap, Yoke Yeow; Yap, Lee Fah; Subramaniam, Selva Kumar; Ong, Cheng Ai; Tan, Tee Yong; Khoo, Alan Soo Beng; Ng, Ching Ching.

In: PloS one, Vol. 11, No. 1, e0145774, 05.01.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A genome wide study of copy number variation associated with nasopharyngeal carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci

AU - Low, Joyce Siew Yong

AU - Chin, Yoon Ming

AU - Mushiroda, Taisei

AU - Kubo, Michiaki

AU - Govindasamy, Gopala Krishnan

AU - Pua, Kin Choo

AU - Yap, Yoke Yeow

AU - Yap, Lee Fah

AU - Subramaniam, Selva Kumar

AU - Ong, Cheng Ai

AU - Tan, Tee Yong

AU - Khoo, Alan Soo Beng

AU - Ng, Ching Ching

PY - 2016/1/5

Y1 - 2016/1/5

N2 - Background Nasopharyngeal 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. Methods A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina1 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). Results Six 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. Conclusion Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

AB - Background Nasopharyngeal 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. Methods A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina1 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). Results Six 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. Conclusion Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

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DO - 10.1371/journal.pone.0145774

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