RT Book, Section A1 Cairns, Brad R. A1 Mardis, Elaine R. A2 Kaushansky, Kenneth A2 Prchal, Josef T. A2 Burns, Linda J. A2 Lichtman, Marshall A. A2 Levi, Marcel A2 Linch, David C. SR Print(0) ID 1178736682 T1 Genomics and Epigenomics T2 Williams Hematology, 10e YR 2021 FD 2021 PB McGraw-Hill Education PP New York, NY SN 9781260464122 LK hemonc.mhmedical.com/content.aspx?aid=1178736682 RD 2024/11/01 AB SUMMARYThe cytogenetic examination of leukemia chromosomes provided the first lines of evidence that cancer was a disease of the genome, supported by the identification of chromosomal translocations that were diagnostic for different leukemia types. These methods gained refinement in the era of whole-genome microarrays and comparative genome hybridization. In the past decade, the application of next-generation sequencing to cancer genome analysis has brought increasing molecular resolution to identifying a myriad of cancer-driving mechanisms, including recurrently altered genes that result from simple nonsynonymous point mutations, insertions or deletions of a few nucleotides (indels), and copy number alterations and other structural variants (translocations and inversions as well as chromosomal arm-level amplifications and deletions) that change the amounts and functions of proteins encoded therein. In addition, similar approaches have uncovered evidence for altered DNA methylation or chromatin packaging caused by differential histone modifications or mutations in chromatin remodelers, DNA methylation regulators, histone modification enzymes, and metabolic enzymes affecting epigenetic cofactors, generally referred to as “epigenomic” modifications. These changes impact cancer-specific gene expression by controlling the density and positioning of nucleosomes and by the use of histone- and DNA-modifying enzymes. Taken together, these different DNA alterations contribute to cancer onset and progression by altering protein function, abundance, or interactions at the level of cellular pathways to arrive at proteomes that promote proliferation, survival, escape from checkpoint controls, and metabolic adaptability. This chapter focuses on examples of technological and analytical approaches used to characterize genomic and epigenomic alterations in hematologic malignancies and their use in research as well as in clinical diagnosis and therapeutic decision making.