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.

Genomic Profiling of a Large Set of Diverse Pediatric Cancers Identifies Known and Novel Mutations across Tumor Spectra.

Abstract: Pediatric cancers are generally characterized by low mutational burden and few recurrently mutated genes. Recent studies suggest that genomic alterations may help guide treatment decisions and clinical trial selection. Here, we describe genomic profiles from 1,215 pediatric tumors representing sarcomas, extracranial embryonal tumors, brain tumors, hematologic malignancies, carcinomas, and gonadal tumors. Comparable published datasets identified similar frequencies of clinically relevant alterations, validating this dataset as biologically relevant. We identified novel ALK fusions in a neuroblastoma (BEND5-ALK) and an astrocytoma (PPP1CB-ALK), novel BRAF fusions in an astrocytoma (BCAS1-BRAF) and a ganglioglioma (TMEM106B-BRAF), and a novel PAX3-GLI2 fusion in a rhabdomyosarcoma. Previously characterized ALK, NTRK1, and PAX3 fusions were observed in unexpected malignancies, challenging the "disease-specific" alterations paradigm. Finally, we identified recurrent variants of unknown significance in MLL3 and PRSS1 predicted to have functional impact. Data from these 1,215 tumors are publicly available for discovery and validation. Cancer Res; 77(2); 509-19. ©2017 AACR.

Molecular and clinicopathologic features of gliomas harboring NTRK fusions.

Abstract: Fusions involving neurotrophic tyrosine receptor kinase (NTRK) genes are detected in ≤2% of gliomas and can promote gliomagenesis. The remarkable therapeutic efficacy of TRK inhibitors, which are among the first Food and Drug Administration-approved targeted therapies for NTRK-fused gliomas, has generated significant clinical interest in characterizing these tumors. In this multi-institutional retrospective study of 42 gliomas with NTRK fusions, next generation DNA sequencing (n = 41), next generation RNA sequencing (n = 1), RNA-sequencing fusion panel (n = 16), methylation profile analysis (n = 18), and histologic evaluation (n = 42) were performed. All infantile NTRK-fused gliomas (n = 7) had high-grade histology and, with one exception, no other significant genetic alterations. Pediatric NTRK-fused gliomas (n = 13) typically involved NTRK2, ranged from low- to high-histologic grade, and demonstrated histologic overlap with desmoplastic infantile ganglioglioma, pilocytic astrocytoma, ganglioglioma, and glioblastoma, among other entities, but they rarely matched with high confidence to known methylation class families or with each other; alterations involving ATRX, PTEN, and CDKN2A/2B were present in a subset of cases. Adult NTRK-fused gliomas (n = 22) typically involved NTRK1 and had predominantly high-grade histology; genetic alterations involving IDH1, ATRX, TP53, PTEN, TERT promoter, RB1, CDKN2A/2B, NF1, and polysomy 7 were common. Unsupervised principal component analysis of methylation profiles demonstrated no obvious grouping by histologic grade, NTRK gene involved, or age group. KEGG pathway analysis detected methylation differences in genes involved in PI3K/AKT, MAPK, and other pathways. In summary, the study highlights the clinical, histologic, and molecular heterogeneity of NTRK-fused gliomas, particularly when stratified by age group.

Biomarker-Based Prediction of Response to Therapy for Colorectal Cancer: Current Perspective

Abstract: The diagnosis and management of colorectal cancer (CRC) has been impacted by the discovery and validation of a wide variety of biomarkers designed to facilitate a personalized approach for the treatment of the disease. Recently, CRC has been reclassified based on molecular analyses of various genes and proteins capable of separating morphologic types of tumors into molecular categories. At the same time, a number of new prognostic and predictive single genes and proteins have been discovered that are designed to reflect sensitivity and/or resistance to existing therapies. Multigene predictors have also been developed to predict the risk of relapse for intermediate-stage CRC after completion of surgical extirpation. More recently, a number of biomarkers tested by a variety of methods have been proposed as specific predictors of chemotherapy and radiotherapy response. Other markers have been successfully used to predict toxic effects of standard therapies. In this review, a series of novel biomarkers are considered and compared with standard-of-care markers for their potential use as pharmacogenomic and pharmacogenetic predictors of disease outcome.