Institution
Foundation Medicine
About: Foundation Medicine is a based out in . It is known for research contribution in the topics: Cancer & Targeted therapy. The organization has 430 authors who have published 1085 publications receiving 41789 citations.
Topics: Cancer, Targeted therapy, Lung cancer, Breast cancer, KRAS
Papers
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TL;DR: Comprehensive genomic profiling highlights the promise of identifying clinically relevant genomic alterations in both ESCC and EAC and suggests new avenues for molecularly directed therapies in esophageal cancer.
Abstract: Background.
Esophageal squamous cell carcinomas (ESCCs) and esophageal adenocarcinomas (EACs) account for >95% of esophageal malignancies and represent a major global health burden. ESCC is the dominant histology globally but represents a minority of U.S. cases, with EAC accounting for the majority of U.S. cases. The patient outcomes for advanced ESCC and EAC are poor, and new therapeutic options are needed. Using a sensitive sequencing assay, we compared the genomic profiles of ESCC and EAC with attention to identification of therapeutically relevant genomic alterations.
78 citations
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TL;DR: This is the first comprehensive genomic analysis of ASCC, and the results suggest new therapeutic approaches andDiffering genomic profiles between HPV-associated and HPV-negative ASCC warrants further investigation and may require novel therapeutic and preventive strategies.
78 citations
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TL;DR: CGP is practical and facilitates implementation of the NCCN guidelines for NSCLC by enabling simultaneous detection of GAs involving all seven driver oncogenes and KRAS and identifies patients with "pan-negative" lung AD who may benefit from enrollment in mechanism-driven clinical trials.
Abstract: Background The National Comprehensive Cancer Network (NCCN) guidelines for patients with metastatic non-small cell lung cancer (NSCLC) recommend testing for EGFR, BRAF, ERBB2, and MET mutations; ALK, ROS1, and RET rearrangements; and MET amplification. We investigated the feasibility and utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) test, in clinical practice. Methods CGP was performed to a mean coverage depth of 576× on 6,832 consecutive cases of NSCLC (2012-2015). Genomic alterations (GAs) (point mutations, small indels, copy number changes, and rearrangements) involving EGFR, ALK, BRAF, ERBB2, MET, ROS1, RET, and KRAS were recorded. We also evaluated lung adenocarcinoma (AD) cases without GAs, involving these eight genes. Results The median age of the patients was 64 years (range: 13-88 years) and 53% were female. Among the patients studied, 4,876 (71%) harbored at least one GA involving EGFR (20%), ALK (4.1%), BRAF (5.7%), ERBB2 (6.0%), MET (5.6%), ROS1 (1.5%), RET (2.4%), or KRAS (32%). In the remaining cohort of lung AD without these known drivers, 273 cancer-related genes were altered in at least 0.1% of cases, including STK11 (21%), NF1 (13%), MYC (9.8%), RICTOR (6.4%), PIK3CA (5.4%), CDK4 (4.3%), CCND1 (4.0%), BRCA2 (2.5%), NRAS (2.3%), BRCA1 (1.7%), MAP2K1 (1.2%), HRAS (0.7%), NTRK1 (0.7%), and NTRK3 (0.2%). Conclusion CGP is practical and facilitates implementation of the NCCN guidelines for NSCLC by enabling simultaneous detection of GAs involving all seven driver oncogenes and KRAS. Furthermore, without additional tissue use or cost, CGP identifies patients with "pan-negative" lung AD who may benefit from enrollment in mechanism-driven clinical trials. Implications for practice National Comprehensive Cancer Network guidelines for patients with metastatic non-small cell lung cancer (NSCLC) recommend testing for several genomic alterations (GAs). The feasibility and utility of comprehensive genomic profiling were studied in NSCLC and in lung adenocarcinoma (AD) without GAs. Of patients with NSCLC, 71% harbored at least one GA to a gene listed in the guidelines or KRAS; 273 cancer-related genes were altered in at least 0.1% of the AD cases. Although logistical and administrative hurdles limit the widespread use of next-generation sequencing, the data confirm the feasibility and potential utility of comprehensive genomic profiling in clinical practice.
77 citations
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TL;DR: This case represents the first report of clinical response to targeted therapy in a tumor harboring a DCTN1-ALK fusion protein, and can identify clinical relevant genomic alterations that both direct treatment targeted therapy and help discriminate between similar diagnostic entities.
Abstract: Recurrent, metastatic mesenchymal myxoid tumors of the gynecologic tract present a management challenge as there is minimal evidence to guide systemic therapy Such tumors also present a diagnostic dilemma, as myxoid features are observed in leiomyosarcomas, inflammatory myofibroblastic tumors (IMT), and mesenchymal myxoid tumors Comprehensive genomic profiling was performed in the course of clinical care on a case of a recurrent, metastatic myxoid uterine malignancy (initially diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP)), to guide identify targeted therapeutic options To our knowledge, this case represents the first report of clinical response to targeted therapy in a tumor harboring a DCTN1-ALK fusion protein Hybridization capture of 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from this sample and sequenced to high, uniform coverage Therapy was given in the context of a phase I clinical trial ClinicalTrialsgov Identifier: (
NCT01548144
) Immunostains showed diffuse positivity for ALK1 expression and comprehensive genomic profiling identified an in frame DCTN1-ALK gene fusion The diagnosis of STUMP was revised to that of an IMT with myxoid features The patient was enrolled in a clinical trial and treated with an anaplastic lymphoma kinase (ALK) inhibitor (crizotinib/Xalkori®) and a multikinase VEGF inhibitor (pazopanib/Votrient®) The patient experienced an ongoing partial response (6+ months) by response evaluation criteria in solid tumors (RECIST) 11 criteria For myxoid tumors of the gynecologic tract, comprehensive genomic profiling can identify clinical relevant genomic alterations that both direct treatment targeted therapy and help discriminate between similar diagnostic entities
77 citations
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TL;DR: This report provides the first detailed description of brain metastases in MET exon 14–positive NSCLC and provides preliminary support for the intracranial activity of cabozantinib.
76 citations
Authors
Showing all 430 results
Name | H-index | Papers | Citations |
---|---|---|---|
Bartolome R. Celli | 118 | 650 | 63423 |
Vincent A. Miller | 105 | 647 | 65822 |
Vera J. Suman | 76 | 294 | 35533 |
Adam Brufsky | 74 | 460 | 27570 |
Jeffrey S. Ross | 70 | 347 | 21334 |
Philip J. Stephens | 69 | 236 | 29559 |
Kai Wang | 69 | 1095 | 21841 |
Siraj M. Ali | 65 | 463 | 25639 |
Jeffrey S. Ross | 59 | 343 | 20600 |
Roman Yelensky | 57 | 164 | 15073 |
Doron Lipson | 57 | 180 | 17014 |
Garrett M. Frampton | 55 | 215 | 22373 |
Geoffrey R. Oxnard | 54 | 245 | 14325 |
Brian M. Alexander | 50 | 264 | 9200 |
Jeffrey P. Gregg | 46 | 107 | 4882 |