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.
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.
Authors: Priyadharsini Nagarajan; Maryam M Asgari; Adele C Green; Samantha M Guhan; Sarah T Arron; Charlotte M Proby; Dana E Rollison; Catherine A Harwood; Amanda Ewart Toland Journal: Clin Cancer Res Date: 2018-12-06 Impact factor: 12.531
Authors: Todd C Knepper; Meagan Montesion; Jeffery S Russell; Ethan S Sokol; Garrett M Frampton; Vincent A Miller; Lee A Albacker; Howard L McLeod; Zeynep Eroglu; Nikhil I Khushalani; Vernon K Sondak; Jane L Messina; Michael J Schell; James A DeCaprio; Kenneth Y Tsai; Andrew S Brohl Journal: Clin Cancer Res Date: 2019-08-09 Impact factor: 12.531
Authors: Catherine Zilberg; Matthew Weicai Lee; Bing Yu; Bruce Ashford; Spiridoula Kraitsek; Marie Ranson; Kerwin Shannon; Mark Cowley; N Gopalakrishna Iyer; Carsten E Palme; Sydney Ch'ng; Tsu-Hui Hubert Low; Sandra O'Toole; Jonathan R Clark; Ruta Gupta Journal: Mod Pathol Date: 2017-10-06 Impact factor: 7.842
Authors: William N William; Lei Feng; Renata Ferrarotto; Lawrence Ginsberg; Merrill Kies; Scott Lippman; Bonnie Glisson; Edward S Kim Journal: J Am Acad Dermatol Date: 2017-09-28 Impact factor: 11.527
Authors: Timothy J Eviston; Elahe Minaei; Simon A Mueller; Navid Ahmadi; Bruce Ashford; Jonathan R Clark; Nicholas West; Ping Zhang; Ruta Gupta; Marie Ranson Journal: Sci Rep Date: 2021-06-23 Impact factor: 4.379