TY - JOUR
T1 - NSD1- A nd NSD2-damaging mutations define a subset of laryngeal tumors with favorable prognosis
AU - Peri, Suraj
AU - Izumchenko, Evgeny
AU - Schubert, Adrian D.
AU - Slifker, Michael J.
AU - Ruth, Karen
AU - Serebriiskii, Ilya G.
AU - Guo, Theresa
AU - Burtness, Barbara A.
AU - Mehra, Ranee
AU - Ross, Eric A.
AU - Sidransky, David
AU - Golemis, Erica A.
N1 - Funding Information:
We were supported by NCI Core Grant P30 CA006927 (to Fox Chase Cancer Center), NCI CA181287, and the Don Devlin Fund (to E.A.G.), pilot Genomics Funding from Temple University and support from the Beck family (to S.P. and E.A.G.), Swiss Cancer League BIL KLS-3649-02-2015 (to A.D.S.), and NIH grant SPORE P50 DE019032 (to D. S.). We thank Anna Nikonova, Emmanuelle Nicholas, and members of Biosample Repository Facility of Fox Chase Cancer Center for their extensive support.
Funding Information:
We were supported by NCI Core Grant P30 CA006927 (to Fox Chase Cancer Center), NCI CA181287, and the Don Devlin Fund.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-017-01877-7
DO - 10.1038/s41467-017-01877-7
M3 - Article
C2 - 29176703
AN - SCOPUS:85034955204
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1772
ER -