Evaluation of 122 advanced‐stage cutaneous squamous cell carcinomas by comprehensive genomic profiling opens the door for new routes to targeted therapies

• Published in: Cancer 2016-01, Vol.122 (2), p.249-257
• Main Authors: Al‐Rohil, Rami N., Tarasen, Ashley J., Carlson, J. Andrew, Wang, Kai, Johnson, Adrienne, Yelensky, Roman, Lipson, Doron, Elvin, Julia A., Vergilio, Jo‐Anne, Ali, Siraj M., Suh, James, Miller, Vincent A., Stephens, Philip J., Ganesan, Prasanth, Janku, Filip, Karp, Daniel D., Subbiah, Vivek, Mihm, Martin C., Ross, Jeffrey S.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; Cohort Studies; cutaneous squamous cell carcinoma; Female; Follow-Up Studies; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; genomic alterations; genomic profiling; Genomics; Humans; Male; Middle Aged; Molecular Targeted Therapy - methods; Neoplasm Invasiveness - pathology; Neoplasm Staging; next‐generation sequencing; Retrospective Studies; Risk Assessment; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Skin Neoplasms - therapy; Treatment Outcome; Young Adult
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.29738

BACKGROUND The authors hypothesized that comprehensive genomic profiling of advanced‐stage cutaneous squamous cell carcinoma (cSCC) could identify genomic‐derived drug targets of therapy for patients with conventional therapy‐resistant disease. METHODS Comprehensive genomic profiling of 315 cancer genes was applied to 50 ng of DNA from 122 cSCC cases for the evaluation of all classes of genomic alterations (GAs). Clinically relevant genomic alterations (CRGAs) were defined as those identifying anticancer drugs on the market or in registered clinical trials. RESULTS There were 21 women (17%) and 101 men (83%) with a median age of 64.9 years (range, 21‐87 years). Eleven cSCC cases (9%) were histologic AJCC grade 1, 69 (57%) were grade 2, and 42 (34%) were grade 3. The primary cSCC was used for sequencing in 77 cases (63%). Metastatic lesions were sequenced in 37% of cases. There were 1120 total GAs identified (average of 9.2 GAs per tumor), with 100% of cases harboring at least 1 alteration. Of the 122 cSCCs, 107 (88%) harbored at least 1 CRGA (2.5 CRGAs per cSCC) includingNOTCH1 (43%); patched 1 (PTCH1) (11%); BRCA2 (10%); HRAS (8%); ataxia telangiectasia mutated (ATM) (7%); erb‐B2 receptor tyrosine kinase 4 (ERBB4) (7%); neurofibromatosis type 1 (NF1) (7%); erb‐B2 receptor tyrosine kinase 2 (ERBB2) (6%); phosphatidylinositol‐4,5‐bisphosphate 3‐kinase, catalytic subunit alpha (PIK3CA) (6%); cyclin D1 (CCND1) (6%); epidermal growth factor receptor (EGFR) (5%); and F‐box and WD repeat domain containing 7, E3 ubiquitin protein ligase (FBXW7) (5%). CONCLUSIONS In the current study, approximately 88% of patients with cSCC were found to harbor clinically relevant GAs that have the potential to guide the treatment of patients with advanced‐stage tumors with targeted therapeutic agents. Cancer 2016;122:249–257. © 2015 American Cancer Society. The current study highlights the mutational landscape in 122 cases of recurrent and refractory cutaneous squamous cell carcinoma and is focused on the discovery of genomic targets that have the potential to guide targeted therapy selection for patients with advanced and metastatic disease. In 88% of the 122 patients reported herein, comprehensive genomic profiling appears to be associated with the detection of clinically relevant genomic alterations capable of guiding therapeutic decisions.