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

Peri, Suraj; Izumchenko, Evgeny; Schubert, Adrian; Slifker, Michael J; Ruth, Karen; Serebriiskii, Ilya G; Guo, Theresa; Burtness, Barbara A; Mehra, Ranee; Ross, Eric A; Sidransky, David; Golemis, Erica A (2017). NSD1- and NSD2-damaging mutations define a subset of laryngeal tumors with favorable prognosis. Nature communications, 8(1), p. 1772. Nature Publishing Group 10.1038/s41467-017-01877-7

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ear, Nose and Throat Disorders (ENT)

UniBE Contributor:

Schubert, Adrian

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Stefan Weder

Date Deposited:

27 Feb 2018 11:57

Last Modified:

24 Oct 2019 04:17

Publisher DOI:

10.1038/s41467-017-01877-7

PubMed ID:

29176703

BORIS DOI:

10.7892/boris.110918

URI:

https://boris.unibe.ch/id/eprint/110918

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