title: Evaluation of 122 advanced-stage cutaneous squamous cell carcinomas by comprehensive genomic profiling opens the door for new routes to targeted therapies.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York.|Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Investigational Cancer Therapeutics (Phase 1 Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rami N
authors.initials: RN
authors.lastname: Al-Rohil
authors.affiliation: Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York.
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Tarasen
authors.affiliation: Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York.
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Carlson
authors.affiliation: Foundation Medicine Inc, Cambridge, Massachusetts.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Foundation Medicine Inc, Cambridge, Massachusetts.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Johnson
authors.affiliation: Foundation Medicine Inc, Cambridge, Massachusetts.
authors.forename: Roman
authors.initials: R
authors.lastname: Yelensky
authors.affiliation: Foundation Medicine Inc, Cambridge, Massachusetts.
authors.forename: Doron
authors.initials: D
authors.lastname: Lipson
authors.affiliation: Foundation Medicine Inc, Cambridge, Massachusetts.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Elvin
authors.affiliation: Foundation Medicine Inc, Cambridge, Massachusetts.
authors.forename: Jo-Anne
authors.initials: JA
authors.lastname: Vergilio
authors.affiliation: Foundation Medicine Inc, Cambridge, Massachusetts.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Foundation Medicine Inc, Cambridge, Massachusetts.
authors.forename: James
authors.initials: J
authors.lastname: Suh
authors.affiliation: Foundation Medicine Inc, Cambridge, Massachusetts.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.affiliation: Foundation Medicine Inc, Cambridge, Massachusetts.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Investigational Cancer Therapeutics (Phase 1 Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Prasanth
authors.initials: P
authors.lastname: Ganesan
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Investigational Cancer Therapeutics (Phase 1 Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Investigational Cancer Therapeutics (Phase 1 Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Karp
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Investigational Cancer Therapeutics (Phase 1 Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Vivek
authors.initials: V
authors.lastname: Subbiah
authors.affiliation: Department of Dermatology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Mihm
authors.affiliation: Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York.|Foundation Medicine Inc, Cambridge, Massachusetts.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D012189:Retrospective Studies; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome; D055815:Young Adult
keywords: cutaneous squamous cell carcinoma; genomic alterations; genomic profiling; next-generation sequencing