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Evaluation of 122 advanced-stage cutaneous squamous cell carcinomas by comprehensive genomic profiling opens the door for new routes to targeted therapies.
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.
Afiliação
  • Al-Rohil RN; Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York.
  • Tarasen AJ; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Carlson JA; Department of Investigational Cancer Therapeutics (Phase 1 Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Wang K; Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York.
  • Johnson A; Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York.
  • Yelensky R; Foundation Medicine Inc, Cambridge, Massachusetts.
  • Lipson D; Foundation Medicine Inc, Cambridge, Massachusetts.
  • Elvin JA; Foundation Medicine Inc, Cambridge, Massachusetts.
  • Vergilio JA; Foundation Medicine Inc, Cambridge, Massachusetts.
  • Ali SM; Foundation Medicine Inc, Cambridge, Massachusetts.
  • Suh J; Foundation Medicine Inc, Cambridge, Massachusetts.
  • Miller VA; Foundation Medicine Inc, Cambridge, Massachusetts.
  • Stephens PJ; Foundation Medicine Inc, Cambridge, Massachusetts.
  • Ganesan P; Foundation Medicine Inc, Cambridge, Massachusetts.
  • Janku F; Foundation Medicine Inc, Cambridge, Massachusetts.
  • Karp DD; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Subbiah V; Department of Investigational Cancer Therapeutics (Phase 1 Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Mihm MC; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Ross JS; Department of Investigational Cancer Therapeutics (Phase 1 Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer ; 122(2): 249-57, 2016 Jan 15.
Article em En | MEDLINE | ID: mdl-26479420
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Carcinoma de Células Escamosas / Perfilação da Expressão Gênica / Terapia de Alvo Molecular Tipo de estudo: Etiology_studies / Evaluation_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Carcinoma de Células Escamosas / Perfilação da Expressão Gênica / Terapia de Alvo Molecular Tipo de estudo: Etiology_studies / Evaluation_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Ano de publicação: 2016 Tipo de documento: Article