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Article: Whole-exome sequencing identifies multiple loss-of-function mutations of NF-κB pathway regulators in nasopharyngeal carcinoma

TitleWhole-exome sequencing identifies multiple loss-of-function mutations of NF-κB pathway regulators in nasopharyngeal carcinoma
Authors
KeywordsSomatic mutation landscape
Whole-exome sequencing
NF-κB signaling
Nasopharyngeal carcinoma
APOBEC-mediated signature
Issue Date2016
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2016, v. 113, n. 40, p. 11283-11288 How to Cite?
AbstractNasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing. An APOBEC cytidine deaminase mutagenesis signature was revealed in the somatic mutations. Noticeably, multiple loss-of-function mutations were identified in several NF-κB signaling negative regulators NFKBIA, CYLD, and TNFAIP3. Functional studies confirmed that inhibition of NFKBIA had a significant impact on NF-κB activity and NPC cell growth. The identified loss-of-function mutations in NFKBIA leading to protein truncation contributed to the altered NF-κB activity, which is critical for NPC tumorigenesis. In addition, somatic mutations were found in several cancer-relevant pathways, including cell cycle-phase transition, cell death, EBV infection, and viral carcinogenesis. These data provide an enhanced road map for understanding the molecular basis underlying NPC.
Persistent Identifierhttp://hdl.handle.net/10722/234555
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorZheng, H-
dc.contributor.authorDai, W-
dc.contributor.authorCheung, AKL-
dc.contributor.authorKo, JMY-
dc.contributor.authorKan, PQR-
dc.contributor.authorWong, WY-
dc.contributor.authorLeong, ML-
dc.contributor.authorDeng, M-
dc.contributor.authorKwok, CTT-
dc.contributor.authorChan, YW-
dc.contributor.authorKwong, DLW-
dc.contributor.authorLee, WMA-
dc.contributor.authorNg, WT-
dc.contributor.authorNgan, RKC-
dc.contributor.authorYau, CC-
dc.contributor.authorTung, S-
dc.contributor.authorLee, VHF-
dc.contributor.authorLam, KO-
dc.contributor.authorKwan, CK-
dc.contributor.authorLi, WS-
dc.contributor.authorYau, S-
dc.contributor.authorChan, KW-
dc.contributor.authorLung, ML-
dc.date.accessioned2016-10-14T13:47:38Z-
dc.date.available2016-10-14T13:47:38Z-
dc.date.issued2016-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2016, v. 113, n. 40, p. 11283-11288-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/234555-
dc.description.abstractNasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing. An APOBEC cytidine deaminase mutagenesis signature was revealed in the somatic mutations. Noticeably, multiple loss-of-function mutations were identified in several NF-κB signaling negative regulators NFKBIA, CYLD, and TNFAIP3. Functional studies confirmed that inhibition of NFKBIA had a significant impact on NF-κB activity and NPC cell growth. The identified loss-of-function mutations in NFKBIA leading to protein truncation contributed to the altered NF-κB activity, which is critical for NPC tumorigenesis. In addition, somatic mutations were found in several cancer-relevant pathways, including cell cycle-phase transition, cell death, EBV infection, and viral carcinogenesis. These data provide an enhanced road map for understanding the molecular basis underlying NPC.-
dc.languageeng-
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.-
dc.subjectSomatic mutation landscape-
dc.subjectWhole-exome sequencing-
dc.subjectNF-κB signaling-
dc.subjectNasopharyngeal carcinoma-
dc.subjectAPOBEC-mediated signature-
dc.titleWhole-exome sequencing identifies multiple loss-of-function mutations of NF-κB pathway regulators in nasopharyngeal carcinoma-
dc.typeArticle-
dc.identifier.emailDai, W: weidai2@hku.hk-
dc.identifier.emailCheung, AKL: arthurhk@hku.hk-
dc.identifier.emailKo, JMY: joko@hku.hk-
dc.identifier.emailWong, WY: bonniewongwy@hku.hk-
dc.identifier.emailKwok, CTT: cttommy@HKUCC-COM.hku.hk-
dc.identifier.emailChan, YW: jywchan1@hku.hk-
dc.identifier.emailKwong, DLW: dlwkwong@hku.hk-
dc.identifier.emailLee, WMA: awmlee@hkucc.hku.hk-
dc.identifier.emailLee, VHF: vhflee@hku.hk-
dc.identifier.emailLam, KO: lamkaon@hku.hk-
dc.identifier.emailChan, KW: kwchan@pathology.hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.authorityDai, W=rp02146-
dc.identifier.authorityCheung, AKL=rp01769-
dc.identifier.authorityKo, JMY=rp02011-
dc.identifier.authorityChan, YW=rp01314-
dc.identifier.authorityKwong, DLW=rp00414-
dc.identifier.authorityLee, WMA=rp02056-
dc.identifier.authorityLee, VHF=rp00264-
dc.identifier.authorityLam, KO=rp01501-
dc.identifier.authorityChan, KW=rp00330-
dc.identifier.authorityLung, ML=rp00300-
dc.identifier.doi10.1073/pnas.1607606113-
dc.identifier.pmid27647909-
dc.identifier.pmcidPMC5056105-
dc.identifier.scopuseid_2-s2.0-84989819048-
dc.identifier.hkuros269275-
dc.identifier.volume113-
dc.identifier.issue40-
dc.identifier.spage11283-
dc.identifier.epage11288-
dc.publisher.placeUnited States-

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