Comparing Genomic Landscapes of Oral and Cutaneous Squamous Cell Carcinoma of the Head and Neck: Quest for Novel Diagnostic Markers

Ruta Gupta; Dario Strbenac; Laveniya Satgunaseelan; Veronica Ka-Yan Cheung; Harini Narayanappa; Bruce Ashford; Jenny Mitchell; Amarinder Thind; Carsten E Palme; Sydney Ch'ng; Tsu-Hui Hubert Low; James Wykes; Cali E Willet; Tracy Chew; Jean Yang; Marie Ranson; Jonathan R Clark

doi:10.1016/j.modpat.2023.100190

Comparing Genomic Landscapes of Oral and Cutaneous Squamous Cell Carcinoma of the Head and Neck: Quest for Novel Diagnostic Markers

Mod Pathol. 2023 Aug;36(8):100190. doi: 10.1016/j.modpat.2023.100190. Epub 2023 Apr 18.

Authors

Ruta Gupta¹, Dario Strbenac², Laveniya Satgunaseelan³, Veronica Ka-Yan Cheung³, Harini Narayanappa⁴, Bruce Ashford⁵, Jenny Mitchell⁵, Amarinder Thind⁶, Carsten E Palme⁷, Sydney Ch'ng⁸, Tsu-Hui Hubert Low⁹, James Wykes¹⁰, Cali E Willet¹¹, Tracy Chew¹¹, Jean Yang², Marie Ranson¹², Jonathan R Clark¹³

Affiliations

¹ Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: Ruta.Gupta@health.nsw.gov.au.
² School of Mathematics and Statistics, The University of Sydney, Sydney, New South Wales, Australia; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
³ Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, New South Wales, Australia.
⁴ Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
⁵ Graduate School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia; Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia; Illawarra Shoalhaven Local Health District, Wollongong, New South Wales, Australia.
⁶ Graduate School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia; Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia.
⁷ Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, New South Wales, Australia; Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.
⁸ Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, New South Wales, Australia; Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia; Department of Plastic and Reconstructive Surgery, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, New South Wales, Australia; Royal Prince Alfred Institute of Academic Surgery, Sydney Local Health District, Sydney, New South Wales, Australia.
⁹ Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, New South Wales, Australia; Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia; Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
¹⁰ Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.
¹¹ Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia; Sydney Informatics Hub, Core Research Facilities, The University of Sydney, Sydney, New South Wales, Australia.
¹² Graduate School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia; Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia; School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, New South Wales, Australia.
¹³ Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, New South Wales, Australia; Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia; Royal Prince Alfred Institute of Academic Surgery, Sydney Local Health District, Sydney, New South Wales, Australia.

PMID: 37080394
DOI: 10.1016/j.modpat.2023.100190

Abstract

Squamous cell carcinoma is the most common head and neck malignancy arising from the oral mucosa and the skin. The histologic and immunohistochemical features of oral squamous cell carcinoma (OSCC) and head and neck cutaneous squamous cell carcinoma (HNcSCC) are similar, making it difficult to identify the primary site in cases of metastases. With the advent of immunotherapy, reliable distinction of OSCC and HNcSCC at metastatic sites has important treatment and prognostic implications. Here, we investigate and compare the genomic landscape of OSCC and HNcSCC to identify diagnostically useful biomarkers. Whole-genome sequencing data from 57 OSCC and 41 HNcSCC patients were obtained for tumor and matched normal samples. Tumor mutation burden (TMB), Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, frequent chromosomal alterations, somatic single nucleotide, and copy number variations were analyzed. The median TMB of 3.75 in primary OSCC was significantly lower (P < .001) than that of 147.51 mutations/Mb in primary HNcSCC. The COSMIC mutation signatures were significantly different (P < .001) between OSCC and HNcSCC. OSCC showed COSMIC single-base substitution (SBS) mutation signature 1 and AID/APOBEC activity-associated signature 2 and/or 13. All except 1 HNcSCC from hair-bearing scalp showed UV damage-associated COSMIC SBS mutation signature 7. Both OSCC and HNcSCC demonstrated a predominance of tumor suppressor gene mutations, predominantly TP53. The most frequently mutated oncogenes were PIK3CA and MUC4 in OSCC and HNcSCC, respectively. The metastases of OSCC and HNcSCC demonstrated TMB and COSMIC SBS mutation signatures similar to their primary counterparts. The combination of high TMB and UV signature in a metastatic keratinizing squamous cell carcinoma suggests HNcSCC as the primary site and may also facilitate decisions regarding immunotherapy. HNcSCC and OSCC show distinct genomic profiles despite histologic and immunohistochemical similarities. Their genomic characteristics may underlie differences in behavior and guide treatment decisions in recurrent and metastatic settings.

Keywords: cutaneous; head and neck; keratinizing squamous cell carcinoma; mutation signature; tumor mutation burden; whole-genome sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics
Carcinoma, Squamous Cell* / genetics
Carcinoma, Squamous Cell* / pathology
DNA Copy Number Variations
Genomics
Head and Neck Neoplasms* / genetics
Humans
Mouth Neoplasms* / pathology
Mutation
Skin Neoplasms* / genetics
Skin Neoplasms* / pathology
Squamous Cell Carcinoma of Head and Neck / genetics

Substances

Biomarkers, Tumor