Vulvar Squamous Cell Carcinoma: Comprehensive Genomic Profiling of HPV+ Versus HPV– Forms Reveals Distinct Sets of Potentially Actionable Molecular Targets
| Autor: | Jeff M Venstrom, Molly McLaughlin-Drubin, Jonathan Keith Killian, Brian M. Alexander, Radwa Sharaf, Nikunj Shah, Helen Toma, Jeffrey S. Ross, Rachel L. Erlich, Mark C. Mochel, Adrienne J Werth, Amanda Hemmerich, Julia A. Elvin, Dean Pavlick, Kevin Jon Williams, Ethan Sokol, Douglas I. Lin, Julie Y. Tse, Eric Allan Severson, Shakti H. Ramkissoon, Meagan Montesion, Erik A. Williams, Natalie Danziger |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Genomic profiling Vulvar Squamous Cell Carcinoma Biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology 030220 oncology & carcinogenesis Original Reports Molecular targets Cancer research Basal cell Human papillomavirus |
| Zdroj: | JCO Precision Oncology |
| ISSN: | 2473-4284 |
| Popis: | PURPOSE Vulvar squamous cell carcinoma (vSCC) encompasses two predominant variants: one associated with detectable high-risk strains of human papillomavirus (hrHPV) and a second form often occurring in the context of chronic dermatitis in postmenopausal women. Genomic assessment of a large-scale cohort of patients with aggressive vSCC may identify distinct mutational signatures. MATERIALS AND METHODS Tumor samples from a total of 280 patients with vSCC underwent hybridization capture with analysis of up to 406 cancer-related genes. Human papillomavirus (HPV) sequences were detected by de novo assembly of nonhuman sequencing reads and aligned to the RefSeq database. Immunohistochemistry for programmed death-ligand 1 (PD-L1) was assessed. RESULTS One hundred two of 280 vSCCs (36%) contained hrHPV sequences, predominantly HPV 16 (88%). The HPV-positive (HPV+) group was significantly younger (median age, 59 v 64 years; P = .001). Compared with HPV-negative (HPV–) vSCCs, HPV+ tumors showed more frequent pathogenic alterations in PIK3CA (31% v 16%; P = .004), PTEN (14% v 2%; P < .0001), EP300 (14% v 1%; P < .0001), STK11 (14% v 1%; P < .0001), AR (5% v 0%; P = .006), and FBXW7 (10% v 3%; P = .03). In contrast, HPV– vSCCs showed more alterations in TP53 (83% v 6%; P < .0001), TERTp (71% v 9%; P < .0001), CDKN2A (55% v 2%; P < .0001), CCND1 amplification (22% v 2%; P < .0001), FAT1 (25% v 4%; P < .0001), NOTCH1 (19% v 6%; P = .002), and EGFR amplification (11% v 0%; P < .0001), as well as a higher rate of 9p24.1 ( PDL1/PDL2) amplification (5% v 1%) and PD-L1 immunohistochemistry high-positive tumor staining (33% v 9%; P = .04). CONCLUSION Comprehensive molecular profiles of vSCC vary considerably with hrHPV status and may inform patient selection into clinical trials. Sixty-one percent of HPV+ vSCCs had a pathogenic alteration in the PI3K/mTOR pathway, whereas HPV– vSCCs showed alterations in TP53, TERTp, CDKN2A, CCND1, and EGFR, and biomarkers associated with responsiveness to immunotherapy. |
| Databáze: | OpenAIRE |
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