title: Greater than the sum of its parts: single-nucleus sequencing identifies convergent evolution of independent EGFR mutants in GBM.
abstract: Single-cell sequencing approaches are needed to characterize the genomic diversity of complex tumors, shedding light on their evolutionary paths and potentially suggesting more effective therapies. In this issue of Cancer Discovery, Francis and colleagues develop a novel integrative approach to identify distinct tumor subpopulations based on joint detection of clonal and subclonal events from bulk tumor and single-nucleus whole-genome sequencing, allowing them to infer a subclonal architecture. Surprisingly, the authors identify convergent evolution of multiple, mutually exclusive, independent EGFR gain-of-function variants in a single tumor. This study demonstrates the value of integrative single-cell genomics and highlights the biologic primacy of EGFR as an actionable target in glioblastoma.
authors.affiliation: Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, California;
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gini
authors.affiliation: Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, California; Department of Pathology, University of California, San Diego, La Jolla, California. pmischel@ucsd.edu.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Mischel
mesh_terms: D066246:ErbB Receptors / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D059010:Single-Cell Analysis / Q000379:methods*
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
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