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In vivo CRISPR screens reveal potent driver mutations in head and neck cancers

Sampath Kumar Loganathan1, Daniel Schramek1,2

  • 1Centre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

Molecular & Cellular Oncology
|September 18, 2020
PubMed

Insights

Researchers identified 15 new tumor suppressor genes in head and neck cancers (HNSCC). These genes regulate the NOTCH signaling pathway, suggesting NOTCH activation as a potential therapy for many HNSCC patients.

Area of Science:

  • Oncology
  • Cancer Genomics
  • Molecular Biology

Background:

  • Head and neck cancers (HNSCC) exhibit complex genomic alterations.
  • Identifying novel tumor suppressor genes is crucial for understanding HNSCC development.
  • The NOTCH signaling pathway plays a significant role in various cancers.

Purpose of the Study:

  • To investigate the transforming potential of understudied 'long-tail' genes in HNSCC.
  • To identify novel tumor suppressor genes implicated in head and neck cancer.
  • To determine the role of these genes in key cellular signaling pathways.

Main Methods:

  • Genomic analysis of 484 'long-tail' genes recurrently mutated in HNSCC.
  • Functional screening to assess the tumor-suppressive capabilities of identified genes.
  • Pathway analysis to pinpoint convergence on critical signaling networks.

Main Results:

  • Fifteen novel tumor suppressor genes were identified in HNSCC.
  • The most significant hits converged on the regulation of the NOTCH signaling pathway.
  • These findings highlight the importance of NOTCH signaling in HNSCC pathogenesis.

Conclusions:

  • Targeting the NOTCH signaling pathway offers a promising therapeutic strategy for HNSCC.
  • Activating NOTCH signaling could benefit a substantial proportion of head and neck cancer patients.
  • The identified tumor suppressors provide new avenues for HNSCC research and treatment.
Keywords:
HNSCCNotchin vivo CRISPRlong-tail genesmouse models of cancer

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