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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Association of TP53 and CDKN2A Mutation Profile with Tumor Mutation Burden in Head and Neck Cancer
Clinical cancer research, v 28(9), pp 1925-1937
02 May 2022
PMID: 35491653
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a frequently devastating cancer that affects more than a half million people annually worldwide. Although some cases arise from infection with human papillomavirus (HPV), HPV-negative HNSCC is more common, and associated with worse outcome. Advanced HPV-negative HNSCC may be treated with surgery, chemoradiation, targeted therapy, or immune checkpoint inhibition (ICI). There is considerable need for predictive biomarkers for these treatments. Defects in DNA repair capacity and loss of cell-cycle checkpoints sensitize tumors to cytotoxic therapies, and can contribute to phenotypes such as elevated tumor mutation burden (TMB), associated with response to ICI. Mutation of the tumor suppressors and checkpoint mediators TP53 and CDKN2A is common in HPV-negative HNSCC.
To gain insight into the relation of the interaction of TP53 and CDKN2A mutations with TMB in HNSCC, we have analyzed genomic data from 1,669 HPV-negative HNSCC tumors with multiple criteria proposed for assessing the damaging effect of TP53 mutations.
Data analysis established the TP53 and CDKN2A mutation profiles in specific anatomic subsites and suggested that specific categories of TP53 mutations are more likely to associate with CDKN2A mutation or high TMB based on tumor subsite. Intriguingly, the pattern of hotspot mutations in TP53 differed depending on the presence or absence of a cooccurring CDKN2A mutation.
These data emphasize the role of tumor subsite in evaluation of mutational profiles in HNSCC, and link defects in TP53 and CDKN2A to elevated TMB levels in some tumor subgroups.
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Details
- Title
- Association of TP53 and CDKN2A Mutation Profile with Tumor Mutation Burden in Head and Neck Cancer
- Creators
- Alexander Y Deneka - Fox Chase Cancer CenterYasmine Baca - Caris Life Sciences (United States)Ilya G Serebriiskii - Fox Chase Cancer CenterEmmanuelle Nicolas - Fox Chase Cancer CenterMitchell I Parker - Fox Chase Cancer CenterTheodore T Nguyen - Drexel University College of Medicine, Philadelphia, PennsylvaniaJoanne Xiu - Caris Life Sciences (United States)W Michael Korn - Caris Life Sciences (United States)Michael J Demeure - Hoag Memorial Hospital PresbyterianTrisha Wise-Draper - University of CincinnatiAmmar Sukari - The Barbara Ann Karmanos Cancer InstituteBarbara Burtness - Yale Cancer CenterErica A Golemis - Fox Chase Cancer Center
- Publication Details
- Clinical cancer research, v 28(9), pp 1925-1937
- Publisher
- American Association for Cancer Research (AACR)
- Grant note
- P30 CA006927 / NCI NIH HHS F30 GM142263 / NIGMS NIH HHS P50 DE030707 / NIDCR NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine
- Web of Science ID
- WOS:000795669300001
- Scopus ID
- 2-s2.0-85129780980
- Other Identifier
- 991020100091104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology