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Nat Commun. 2017 Nov 24;8(1):1772. doi: 10.1038/s41467-017-01877-7.

NSD1- and NSD2-damaging mutations define a subset of laryngeal tumors with favorable prognosis.

Author information

1
Biostatistics and Bioinformatics Division, Fox Chase Cancer Center, Philadelphia, 19111, PA, USA. suraj.peri@fccc.edu.
2
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
3
Department of Otorhinolaryngology-Head and Neck Surgery, Inselspital, University Hospital and University of Bern, Bern, 3010, Switzerland.
4
Biostatistics and Bioinformatics Division, Fox Chase Cancer Center, Philadelphia, 19111, PA, USA.
5
Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.
6
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
7
Department of Internal Medicine and Developmental Therapeutics Program, Yale Cancer Center, Yale School of Medicine, Yale University, New Haven, CT, 06520, USA.
8
Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA. Erica.golemis@fccc.edu.

Abstract

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.

PMID:
29176703
PMCID:
PMC5701248
DOI:
10.1038/s41467-017-01877-7
[Indexed for MEDLINE]
Free PMC Article

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