Review Series GENOME SEQUENCING AND ITS IMPACT ON HEMATOLOGY Genome sequencing of lymphoid malignancies

The lymphoid malignancies represent a diverse range of tumors characterized by variable stages of maturation ranging from proB or T cells in acute lymphoblastic leukemia (ALL) to cells representative of the lymph node in the non-Hodgkin lymphomas (NHLs) to mature plasma cells in myeloma and related disorders. These disorders have a diverse range of clinical manifestations, sites of organ involvement, and responsiveness to therapy. Somatic genetic alterations are a hallmark of lymphoid malignancies, and it is now known that each tumor type typically harbors a constellation of genetic alterations, including gross chromosomal alterations (aneuploidy and/or chromosomal rearrangements), structural genetic alterations (deletions and gains of DNA), and sequence mutations. Genomic techniques that have identified these alterations may be grouped into three broad categories: (1) cytogenetic studies that have identified structural chromosomal alterations, coupled with limited candidate gene sequencing or structural profiling studies; (2) first-generation genome-wide profiling using array-based comparative genomic hybridization or single nucleotide polymorphism microarrays and gene expression profiling; and (3) second-generation sequencing studies using whole-genome sequencing (WGS), transcriptome sequencing (messenger mRNA [mRNA-seq]) and/or whole-exome sequencing (WES) to more comprehensively define the genomic landscape of these diseases. For each tumor type discussed below, key genetic alterations identified from cytogenetic and firstgeneration genomic profiling studies are presented to provide context for the results of next-generation sequencing (NGS) studies summarized in Table 1. ALL