Improved molecular karyotyping in glioblastoma.

Graphical abstract Highlights • Betaine improves coverage and stability of single cell whole genome amplification (WGA). • Measuring the presence of single copy loci across the genome serves as a proxy for WGA coverage. • Tumor clones containing novel CNVs in cancer driver loci arise during glioma growth. Abstract Uneven replication creates artifacts during whole genome amplification (WGA) that confound molecular karyotype assignment in single cells. Here, we present an improved WGA recipe that increased coverage and detection of copy number variants (CNVs) in single cells. We examined serial resections of glioblastoma (GBM) tumor from the same patient and found low-abundance clones containing CNVs in clinically relevant loci that were not observable using bulk DNA sequencing. We discovered extensive genomic variability in this class of tumor and provide a practical approach for investigating somatic mosaicism. [ABSTRACT FROM AUTHOR]