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Rare driver mutations in head and neck squamous cell carcinomas converge on NOTCH signaling.

Authors :
Loganathan SK
Schleicher K
Malik A
Quevedo R
Langille E
Teng K
Oh RH
Rathod B
Tsai R
Samavarchi-Tehrani P
Pugh TJ
Gingras AC
Schramek D
Source :
Science (New York, N.Y.) [Science] 2020 Mar 13; Vol. 367 (6483), pp. 1264-1269.
Publication Year :
2020

Abstract

In most human cancers, only a few genes are mutated at high frequencies; most are mutated at low frequencies. The functional consequences of these recurrent but infrequent "long tail" mutations are often unknown. We focused on 484 long tail genes in head and neck squamous cell carcinoma (HNSCC) and used in vivo CRISPR to screen for genes that, upon mutation, trigger tumor development in mice. Of the 15 tumor-suppressor genes identified, ADAM10 and AJUBA suppressed HNSCC in a haploinsufficient manner by promoting NOTCH receptor signaling. ADAM10 and AJUBA mutations or monoallelic loss occur in 28% of human HNSCC cases and are mutually exclusive with NOTCH receptor mutations. Our results show that oncogenic mutations in 67% of human HNSCC cases converge onto the NOTCH signaling pathway, making NOTCH inactivation a hallmark of HNSCC.<br /> (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Details

Language :
English
ISSN :
1095-9203
Volume :
367
Issue :
6483
Database :
MEDLINE
Journal :
Science (New York, N.Y.)
Publication Type :
Academic Journal
Accession number :
32165588
Full Text :
https://doi.org/10.1126/science.aax0902