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Peri S , Izumchenko E , Schubert AD , Slifker MJ , Ruth K , Serebriiskii IG , Guo T , Burtness BA , Mehra R , Ross EA , Sidransky D , Golemis EA
NSD1- and NSD2-damaging mutations define a subset of laryngeal tumors with favorable prognosis
Nat Commun. 2017 Nov 24;8(1) :1772
PMID: 29176703    PMCID: PMC5701248   
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Squamous cell carcinomas of the head and neck (SCCHN) affect anatomical sites including the oral cavity, nasal cavity, pharynx, and larynx. Laryngeal cancers are characterized by high recurrence and poor overall survival, and currently lack robust molecular prognostic biomarkers for treatment stratification. Using an algorithm for integrative clustering that simultaneously assesses gene expression, somatic mutation, copy number variation, and methylation, we for the first time identify laryngeal cancer subtypes with distinct prognostic outcomes, and differing from the non-prognostic laryngeal subclasses reported by The Cancer Genome Atlas (TCGA). Although most common laryngeal gene mutations are found in both subclasses, better prognosis is strongly associated with damaging mutations of the methyltransferases NSD1 and NSD2, with findings confirmed in an independent validation cohort consisting of 63 laryngeal cancer patients. Intriguingly, NSD1/2 mutations are not prognostic for nonlaryngeal SCCHN. These results provide an immediately useful clinical metric for patient stratification and prognostication.
2041-1723 Peri, Suraj Izumchenko, Evgeny Schubert, Adrian D ORCID: http://orcid.org/0000-0002-7316-2727 Slifker, Michael J Ruth, Karen Serebriiskii, Ilya G Guo, Theresa Burtness, Barbara A Mehra, Ranee Ross, Eric A Sidransky, David Golemis, Erica A ORCID: http://orcid.org/0000-0003-3618-3673 P30 CA006927/CA/NCI NIH HHS/United States P50 DE019032/DE/NIDCR NIH HHS/United States R21 CA181287/CA/NCI NIH HHS/United States Journal Article England Nat Commun. 2017 Nov 24;8(1):1772. doi: 10.1038/s41467-017-01877-7.