title: High-Throughput Genomic Profiling of Adult Solid Tumors Reveals Novel Insights into Cancer Pathogenesis.
abstract: Genomic profiling is widely predicted to become a standard of care in clinical oncology, but more effective data sharing to accelerate progress in precision medicine will be required. Here, we describe cancer-associated genomic profiles from 18,004 unique adult cancers. The dataset was composed of 162 tumor subtypes including multiple rare and uncommon tumors. Comparison of alteration frequencies to The Cancer Genome Atlas identified some differences and suggested an enrichment of treatment-refractory samples in breast and lung cancer cohorts. To illustrate novelty within the dataset, we surveyed the genomic landscape of rare diseases and identified an increased frequency ofNOTCH1alterations in adenoid cystic carcinomas compared with previous studies. Analysis of tumor suppressor gene patterns revealed disease specificity for certain genes but broad inactivation of others. We identified multiple potentially druggable, novel and known kinase fusions in diseases beyond those in which they are currently recognized. Analysis of variants of unknown significance identified an enrichment ofSMAD4alterations in colon cancer and other rare alterations predicted to have functional impact. Analysis of established, clinically relevant alterations highlighted the spectrum of molecular changes for which testing is currently recommended, as well as opportunities for expansion of indications for use of approved targeted therapies. Overall, this dataset presents a new resource with which to investigate rare alterations and diseases, validate clinical relevance, and identify novel therapeutic targets.Cancer Res; 77(9); 2464-75. ©2017 AACR.
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts. rhartmaier@foundationmedicine.com dlipson@foundationmedicine.com.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Hartmaier
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Albacker
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Juliann
authors.initials: J
authors.lastname: Chmielecki
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Mark
authors.initials: M
authors.lastname: Bailey
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Goldberg
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Shakti
authors.initials: S
authors.lastname: Ramkissoon
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: James
authors.initials: J
authors.lastname: Suh
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Elvin
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Samuel
authors.initials: S
authors.lastname: Chiacchia
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Frampton
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.|Albany Medical College, Albany, New York.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Vincent
authors.initials: V
authors.lastname: Miller
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts. rhartmaier@foundationmedicine.com dlipson@foundationmedicine.com.
authors.forename: Doron
authors.initials: D
authors.lastname: Lipson
mesh_terms: D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020022:Genetic Predisposition to Disease; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D057285:Precision Medicine
chemical_list: D009363:Neoplasm Proteins