Please use this identifier to cite or link to this item: https://doi.org/10.1038/npjgenmed.2016.15
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dc.titleGermline hemizygous deletion of CDKN2A-CDKN2B locus in a patient presenting with Li-Fraumeni syndrome
dc.contributor.authorChan, S.H
dc.contributor.authorLim, W.K
dc.contributor.authorMichalski, S.T
dc.contributor.authorLim, J.Q
dc.contributor.authorIshak, N.D.B
dc.contributor.authorMet-Domestici, M
dc.contributor.authorYoung, C.N.C
dc.contributor.authorVikstrom, K
dc.contributor.authorEsplin, E.D
dc.contributor.authorFulbright, J
dc.contributor.authorAng, M.K
dc.contributor.authorWee, J
dc.contributor.authorSittampalam, K
dc.contributor.authorFarid, M
dc.contributor.authorLincoln, S.E
dc.contributor.authorItahana, K
dc.contributor.authorAbdullah, S
dc.contributor.authorTeh, B.T
dc.contributor.authorNgeow, J
dc.date.accessioned2020-10-22T02:56:48Z
dc.date.available2020-10-22T02:56:48Z
dc.date.issued2016
dc.identifier.citationChan, S.H, Lim, W.K, Michalski, S.T, Lim, J.Q, Ishak, N.D.B, Met-Domestici, M, Young, C.N.C, Vikstrom, K, Esplin, E.D, Fulbright, J, Ang, M.K, Wee, J, Sittampalam, K, Farid, M, Lincoln, S.E, Itahana, K, Abdullah, S, Teh, B.T, Ngeow, J (2016). Germline hemizygous deletion of CDKN2A-CDKN2B locus in a patient presenting with Li-Fraumeni syndrome. npj Genomic Medicine 1 : 16015. ScholarBank@NUS Repository. https://doi.org/10.1038/npjgenmed.2016.15
dc.identifier.issn20567944
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/178902
dc.description.abstractLi-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome usually associated with TP53 germline alterations. Its genetic basis in TP53 wild-Type pedigrees is less understood. Using whole-genome sequencing, we identified a germline hemizygous deletion ablating CDKN2A-CDKN2B in a TP53 wild-Type patient presenting with high-grade sarcoma, laryngeal squamous cell carcinoma and a family history suggestive of LFS. Patient-derived cells demonstrated reduced basal gene and protein expression of the CDKN2A-encoded tumour suppressors p14ARF and p16INK4A with concomitant decrease in p21 and faster cell proliferation, implying potential deregulation of p53-mediated cell cycle control. Review of 13 additional patients with pathogenic CDKN2A variants suggested associations of germline CDKN2A mutations with an expanded spectrum of non-melanoma familial cancers. To our knowledge, this is the first report of a germline gross deletion of the CDKN2A-CDKN2B locus in an LFS family. These findings highlight the potential contribution of germline CDKN2A deletions to cancer predisposition and the importance of interrogating the full extent of CDKN2A locus in clinical testing gene panels. © 2016 Published in partnership with the Center of Excellence in Genomic Medicine Research.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1038/npjgenmed.2016.15
dc.description.sourcetitlenpj Genomic Medicine
dc.description.volume1
dc.description.page16015
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