title: Mutation Profiling of Clinically Advanced Cancers Using Next-Generation Sequencing for Targeted Therapy: A Lifespan Experience.
abstract: The application of modern molecular tests such as next-generation sequencing (NGS) to human malignancies has led to better understanding of tumor biology and the design of targeted molecular therapies. In the research setting, important genomic alterations in tumors have been discovered with potential therapeutic implications but data regarding the impact of this technology in a real world oncology practice is limited. As a result, we decided to review the results of NGS in 144 advanced-stage cancer patients referred to the oncology practices of Lifespan-affiliated centers in Rhode Island. Most cancers revealed genomic alterations in genes commonly mutated in cancer. However, several unexpected genomic alterations were discovered in certain cancers with potential therapeutic intervention. Most cancers contained "actionable" genomic alterations despite being of advanced stage. Our experience demonstrates that application of NGS in the clinical setting contributes both to increasing the therapeutic armamentarium as well as our understanding of tumor biology.
authors.affiliation: Gastrointestinal Pathology Fellow in the Department of Pathology at Lifespan/Rhode Island Hospital.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Friedman
authors.affiliation: Professor of Pathology at the Alpert Medical School of Brown University and Vice Chair of Pathology and Director of Gastrointestinal Pathology at Lifespan/Rhode Island Hospital.
authors.forename: Murray B
authors.initials: MB
authors.lastname: Resnick
authors.affiliation: Director of the Brown University Oncology Group and Professor of Medicine at the Alpert Medical School of Brown University.
authors.forename: Howard
authors.initials: H
authors.lastname: Safran
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*
keywords: Next generation sequencing; actionable; genomic alterations; targeted therapy