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: A comprehensive genomic profiling with targeted next‐generation sequencing panel was performed to test for genomic aberrations in archival tumor samples from patients with Hodgkin lymphoma to identify potentially actionable molecular targets.
Abstract: BACKGROUND The genomic landscape of Hodgkin lymphoma (HL) has been difficult to characterize due to the paucity of neoplastic cells and an abundant microenvironment. Such characterization is needed in order to improve treatment strategies. MATERIALS AND METHODS We performed comprehensive genomic profiling (CGP) using targeted next-generation sequencing on archival formalin-fixed paraffin embedded tumor samples from 63 patients to analyze the landscape of HL. RESULTS CGP was successful for 49/63 archival specimens (78%), and revealed aberrations impacting genes including B2M, TP53, and XPO1 (E571). Of the 34 patients for whom total mutation burden (TMB; mutations/megabase [Mb]) was assessed, 5 (15%) had high TMB (≥20 mutations/Mb), 18 (53%) had intermediate TMB (6-19 mutations/Mb), and 11 (32%) had low TMB (≤5 mutations/Mb). We next tested 13 patients' plasma cell-free DNA with droplet digital polymerase chain reaction for the presence of XPO1 E571 mutation, which was confirmed in the plasma of 31% of patients. In three patients with serially collected plasma samples, XPO1 E571K allelic frequency changes corresponded with changes in tumor size on conventional radiographic imaging. CONCLUSION The study demonstrates that comprehensive genomic profiling of archival Hodgkin lymphoma tumor samples is feasible and leads to the identification of genes that are recurrently mutated and that Hodgkin lymphoma has increased mutation burden in the majority of samples analyzed. Furthermore, tracking of XPO1 E571 mutant allele frequency in a subset of patients may also represent a potential disease-monitoring strategy and warrants further investigation. IMPLICATIONS FOR PRACTICE This study provides the first evidence that comprehensive genomic profiling can be performed to map the genomic landscape of Hodgkin lymphoma and that a subpopulation of patients has mutations in TP53, B2M, XPO1, and other genes. It was found that 15% of patients have high mutation burden, which, in cancers such as melanoma, may indicate sensitivity to immune checkpoint inhibitors, and may thus be explored for Hodgkin lymphoma. Lastly, this work demonstrates that changes in the mutant allele frequency of XPO1 in serially collected plasma cell-free DNA samples correspond with treatment outcomes measured with conventional radiographic imaging.
24 citations
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TL;DR: While recurrent serous ECs were predominantly copy-number high, the authors found no clear prevalence of a specific molecular subtype in endometrioid, clear cell or undifferentiated tumors.
24 citations
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European Organisation for Research and Treatment of Cancer1, Erasmus University Medical Center2, National Institutes of Health3, Wellcome Trust Sanger Institute4, Université Paris-Saclay5, Katholieke Universiteit Leuven6, Food and Drug Administration7, Karolinska Institutet8, MedImmune9, Columbia University Medical Center10, European Bioinformatics Institute11, Merck & Co.12, Duke University13, Harvard University14, Pharmaceuticals and Medical Devices Agency15, Medicines and Healthcare Products Regulatory Agency16, Institute of Cancer Research17, European Medicines Agency18, Mayo Clinic19, University of Cambridge20, Netherlands Cancer Institute21, American Society of Clinical Oncology22, New York State Department of Health23, VU University Medical Center24, Foundation Medicine25
TL;DR: The practical requirements and challenges of developing new precision medicine strategies, based on leveraging complex genomic profiles, as discussed at the Innovation and Biomarkers in Cancer Drug Development meeting are discussed.
24 citations
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TL;DR: It is suggested that TTFields delivered in combination with targeted therapy dabrafenib yielded a remarkable clinical and radiologic response in this recurrent high-grade glioma.
Abstract: Background Gangliogliomas are slow-growing, low-grade central nervous system tumors affecting children and young adults. However, some patients will experience tumor recurrence and/or malignant progression. This article reports on the clinical history, molecular findings, and treatment response in a patient with BRAF V600-mutated high-grade glioma arising from ganglioglioma. Methods Hematoxylin-eosin staining and comprehensive genomic profiling via Foundation One were performed on the tumor sample from a male patient undergoing treatment at the Department of Neuro-Oncology at Baylor University Medical Center. Results The patient was eligible for participation in a clinical trial (ClinicalTrials.gov identifier: NCT00916409) of a tumor treatment fields (TTFields) device, NovoTTF-100A, with concurrent radiation and chemotherapy (CCRT). His disease relapsed 4 months after completion of his CCRT, with MRI showing areas of enhancement. Temozolomide was discontinued and he was offered dabrafenib, an oral selective inhibitor of BRAF V600E, with continued use of NovoTTF. At the time of this report, after 2 years of treatment with dabrafenib and TTFields, the patient shows a durable complete response in all areas with no active lesions or new areas of enhancement. Conclusions This report suggests that TTFields delivered in combination with targeted therapy dabrafenib yielded a remarkable clinical and radiologic response in this recurrent high-grade glioma. Targeted therapy matched to genomic alterations combined with TTFields treatment could provide clinical benefit and should be prospectively explored in the near future.
24 citations
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TL;DR: The findings suggest that a subset of CD30+ ALK− systemic PTCL with anaplastic morphology carry JAK2 rearrangements, some of which appear to show CHL-like morphologic features.
Abstract: Peripheral T-cell lymphoma (PTCL) comprises a heterogenous group of rare mature T-cell neoplasms. While some PTCL subtypes are well-characterized by histology, immunophenotype, and recurrent molecular alterations, others remain incompletely defined. In particular, the distinction between CD30+ PTCL, not otherwise specified and anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma can be subject to disagreement. We describe a series of 6 JAK2 rearrangements occurring in a cohort of 97 CD30+ ALK- PTCL (6%), assembled after identifying an index case of a novel PABPC1-JAK2 fusion in a case of ALK- anaplastic large cell lymphoma with unusual classic Hodgkin lymphoma (CHL)-like features. Fusions were identified using a comprehensive next-generation sequencing based assay performed between 2013 and 2020. Five of 6 cases (83%) showed JAK2 rearrangements with 4 novel partners: TFG, PABPC1, ILF3, and MAP7, and 1 case demonstrated a previously described PCM1-JAK2 fusion. By morphology, all cases showed anaplastic large cells and multinucleated Reed-Sternberg-like cells within a polymorphous inflammatory background with frequent eosinophilia reminiscent of CHL. By immunohistochemistry, atypical large cells expressed CD30 with coexpression of at least 1 T-cell marker, aberrant loss of at least 1 T-cell marker and, in 4 of 5 cases stained (80%), unusual CD15 coexpression. These findings suggest that a subset of CD30+ ALK- systemic PTCL with anaplastic morphology carry JAK2 rearrangements, some of which appear to show CHL-like morphologic features. The presence of JAK2 rearrangements in cases of CD30+ PTCL augments current classification and may provide a therapeutic target via JAK2 inhibition.
24 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 |