title: Genomic Landscape of Malignant Mesotheliomas.
abstract: Understanding the genomic landscape of malignant mesothelioma may identify novel molecular drivers of this ultra-rare disease, which can lead to an expanded roster of targeted therapies and clinical trial options for patients with mesothelioma. We examined the molecular profiles of 42 patients with malignant mesothelioma (including pleural, peritoneal, and pericardial) that were referred by clinicians to be tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory using next-generation sequencing (NGS; 182 or 236 genes). Among 42 patients, there were 116 alterations, with 92 being distinct. The number of genomic alterations per patient ranged from 1 to 5 (median = 3). No two patients had identical molecular portfolios. The most common aberrations were in BAP1 (BRCA1-associated protein 1; 47.6% [20/42]), NF2 (38.1% [16/42]), and CDKN2A/B (loss) (35.7% [15/42]). BAP1 alterations and CDKN2A/B loss were associated with pleural mesothelioma (OR 3.4, P = 0.059 [BAP1] [trend]; OR 5.8, P = 0.01 [CDKN2A/B]). All 42 patients had a molecular abnormality that was potentially actionable (median = three actionable alterations per patient; range, 1 to 5), and, in 40 patients (95.2%), a drug approved by the FDA was applicable. In conclusion, each individual with malignant mesothelioma harbored a unique set of genomic aberrations, suggesting that NGS-based profiling of patients will be needed if patients are to be optimally matched to cognate treatments. All 42 patients had at least one alteration that was, in theory, pharmacologically tractable. Mol Cancer Ther; 15(10); 2498-507. ©2016 AACR.
authors: Department of Medicine, Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UC San Diego Moores Cancer Center, La Jolla, California. smkato@ucsd.edu.
authors: Shumei
authors: S
authors: Kato
authors: N-of-One, Inc., Lexington, Massachusetts.
authors: Brett N
authors: BN
authors: Tomson
authors: N-of-One, Inc., Lexington, Massachusetts.
authors: Timon P H
authors: TP
authors: Buys
authors: N-of-One, Inc., Lexington, Massachusetts.
authors: Sheryl K
authors: SK
authors: Elkin
authors: N-of-One, Inc., Lexington, Massachusetts.
authors: Jennifer L
authors: JL
authors: Carter
authors: Department of Medicine, Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UC San Diego Moores Cancer Center, La Jolla, California.
authors: Razelle
authors: R
authors: Kurzrock
mesh_terms: D014408:Biomarkers, Tumor; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D023281:Genomics / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008654:Mesothelioma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D000086002:Mesothelioma, Malignant; D058990:Molecular Targeted Therapy; D009154:Mutation; D009367:Neoplasm Staging
chemical_list: D014408:Biomarkers, Tumor