title: Reviewing the genetic alterations in high-risk cutaneous squamous cell carcinoma: A search for prognostic markers and therapeutic targets.
abstract: Cutaneous squamous cell carcinoma (SCC) is second only in incidence to basal cell carcinoma (BCC), effecting up to 500 000 people in the United States annually. Metastasis to regional lymph nodes occurs in approximately 5% of cases and imparts significant morbidity. Standard treatment in this group involves a combination of surgery and adjuvant radiation. Currently, there are no clinically useful biomarkers of metastatic potential in primary cutaneous SCC and histological predictors can be unreliable. The high level of mutational burden in normal UV-exposed skin has hampered the search for novel drivers of invasive disease, and indeed metastatic potential. This review outlines the clinical problems in high-risk and metastatic cutaneous SCCs, reviews the known genetic events and molecular mechanisms in high-risk primary cutaneous SCC and metastasis, and identifies avenues for further investigation and potential therapy.
authors.affiliation: School of Biological Sciences, University of Wollongong, Northfields Avenue, Wollongong, New South Wales, Australia.|Illawarra Health and Medical Research Institute (IHMRI), Northfields Avenue, Wollongong, New South Wales, 2522, Australia.|Illawarra and Shoalhaven Local Health District (ISLHD), Loftus Street, Wollongong, New South Wales, 2500, Australia.|Centre for Oncology Education and Research Translation (CONCERT), Liverpool, New South Wales, 2170, Australia.
authors.forename: Bruce G
authors.identifier: 0000-0003-4547-6611
authors.initials: BG
authors.lastname: Ashford
authors.affiliation: Sydney Head and Neck Cancer Institute, Department of Head and Neck Surgery Chris O'Brien Lifehouse, 119-143 Missenden Road, Camperdown, New South Wales, 2050, Australia.|Central Clinical School, the University of Sydney, New South Wales, 2006, Australia.|South Western Clinical School, University of New South Wales, Goulburn Street, Liverpool, New South Wales, 2170, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clark
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales, 2050, Australia.|University of Sydney, New South Wales, 2006, Australia.
authors.forename: Ruta
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Singhealth/Duke-NUS Head and Neck Center, National Cancer Center, Singapore (NCCS), 11 Hospital Drive, Singapore, 169610.
authors.forename: N Gopalakrishna
authors.identifier: 0000-0002-8812-6219
authors.initials: NG
authors.lastname: Iyer
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales, 2050, Australia.|University of Sydney, New South Wales, 2006, Australia.
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.affiliation: Illawarra Health and Medical Research Institute (IHMRI), Northfields Avenue, Wollongong, New South Wales, 2522, Australia.|Centre for Oncology Education and Research Translation (CONCERT), Liverpool, New South Wales, 2170, Australia.|School of Biological Sciences, University of Wollongong, Northfields Avenue, Wollongong, New South Wales, 2522, Australia.
authors.forename: Marie
authors.initials: M
authors.lastname: Ranson
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D014644:Genetic Variation; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods; D009154:Mutation; D009362:Neoplasm Metastasis / Q000473:pathology; D011379:Prognosis; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor
keywords: carcinoma; genomic; high risk; metastasis; skin