Please use this identifier to cite or link to this item: https://hdl.handle.net/1/1591
Title: Is high-risk cutaneous squamous cell carcinoma of the head and neck a suitable candidate for current targeted therapies?
Authors: Zilberg, Catherine ;Lee, M.W.;Kraitsek, S.;Ashford, B.;Shannon, K.;Iyer, N.G.;Ch'ng, S.;Low, T.H.;Palme, C.;Clark, J.;Gupta, R.;Yu, B.
Affliation: Central Coast Local Health District
Gosford Hospital
Issue Date: Jul-2019
Source: 73(1):17-22
Journal title: Journal of Clinical Pathology
Department: Medicine
Abstract: OBJECTIVE: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy, most frequently affecting the head and neck. Treatment often requires surgery and can have significant functional morbidity. Research into disease pathogenesis and second line medical management of cSCC is limited. We assess genetic mutations in high-risk, primary head and neck cutaneous squamous cell carcinomas (HNcSCC) that may hinder or be beneficial for use of targeted therapy in disease management. METHODS: Genetic alterations and variant allele frequencies (VAFs) were analysed using a clinically relevant 48 gene panel in 10 primary high-risk non-metastatic treatment-naive HNcSCC to evaluate applicability of targeted therapeutics. Variants present at all VAFs were evaluated for pathogenicity. Somatic mutation patterns of individual tumours were analysed. RESULTS: High-risk HNcSCC showed a high proportion (82%) of C to T transitions in keeping with ultraviolet-mediated damage. There was significant intratumour genetic heterogeneity in this cohort (MATH scores 20-89) with the two patients <45 years of age showing highest intratumour heterogeneity. TP53 was altered at VAF >22% in all cases, and mutations with highest VAF were observed in tumour suppressor genes in 80%. 70% of cases demonstrated at least one mutation associated with treatment resistance (KIT S821F, KIT T670I, RAS mutations at codons 12 and 13). CONCLUSION: We demonstrate high proportion tumour suppressor loss of function mutations, high intratumour genetic heterogeneity, and presence of well recognised resistance mutations in treatment naive primary HNcSCC. These factors pose challenges for successful utilisation of targeted therapies.
URI: https://elibrary.cclhd.health.nsw.gov.au/cclhdjspui/handle/1/1591
DOI: 10.1136/jclinpath-2019-206038
Pubmed: https://www.ncbi.nlm.nih.gov/pubmed/31300530
ISSN: 0021-9746
Publicaton type: Journal Article
Keywords: Cancer
Genotype
Appears in Collections:Oncology / Cancer

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