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
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science
2016
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| Online Access: | http://psasir.upm.edu.my/id/eprint/17534/1/journal.pone.0145774.PDF |
| _version_ | 1825946029284917248 |
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| author | 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 The Malaysian NPC Study Group, Ng, Ching Ching |
| author_facet | 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 The Malaysian NPC Study Group, Ng, Ching Ching |
| author_sort | Low, Joyce Siew Yong |
| collection | UPM |
| description | 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 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). 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. |
| first_indexed | 2024-03-06T07:40:43Z |
| format | Article |
| id | upm.eprints-17534 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T07:40:43Z |
| publishDate | 2016 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | upm.eprints-175342016-06-08T04:24:05Z http://psasir.upm.edu.my/id/eprint/17534/ 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 The Malaysian NPC Study Group, Ng, Ching Ching 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 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). 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. Public Library of Science 2016 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/17534/1/journal.pone.0145774.PDF Low, Joyce Siew Yong and Chin, Yoon Ming and Mushiroda, Taisei and Kubo, Michiaki 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 The Malaysian NPC Study Group, and Ng, Ching Ching (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, 11 (1). art. no. e0145774. pp. 1-17. ISSN 1932-6203 10.1371/journal.pone.0145774 |
| spellingShingle | 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 The Malaysian NPC Study Group, 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 |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://psasir.upm.edu.my/id/eprint/17534/1/journal.pone.0145774.PDF |
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