High-Throughput Genomic Profiling of Adult Solid Tumors Reveals Novel Insights into Cancer Pathogenesis
| Autor: | Ryan J. Hartmaier, Samuel Chiacchia, Philip J. Stephens, James Suh, Juliann Chmielecki, Shakti H. Ramkissoon, Michael E. Goldberg, Julia A. Elvin, Vincent A. Miller, Doron Lipson, Jeffrey S. Ross, Mark Bailey, Garrett M. Frampton, Jie He, Lee A. Albacker |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Tumor suppressor gene Colorectal cancer Druggability Genomics Disease Biology Bioinformatics 03 medical and health sciences 0302 clinical medicine Neoplasms medicine Humans Genetic Predisposition to Disease Clinical significance Molecular Targeted Therapy Precision Medicine Lung cancer Gene Expression Profiling High-Throughput Nucleotide Sequencing Precision medicine medicine.disease Neoplasm Proteins Gene Expression Regulation Neoplastic 030104 developmental biology Oncology 030220 oncology & carcinogenesis Mutation |
| Zdroj: | Cancer Research. 77:2464-2475 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-16-2479 |
| Popis: | 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 of NOTCH1 alterations 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 of SMAD4 alterations 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. |
| Databáze: | OpenAIRE |
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