St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project: Whole Genome Sequencing of Childhood Hypodiploid Acute Lymphoblastic Leukemia. Homo sapiens

Hypodiploid acute lymphoblastic leukemia (ALL) is an aggressive form of leukemia characterized by multiple whole chromosomal losses and very poor outcome. Here we report an integrative genomic analysis that identifies multiple subtypes of hypodiploid ALL characterized by variation in the degree of aneuploidy, distinct submicroscopic deletions and sequence mutations and gene expression profile. Near haploid ALL cases (24-31 chromosomes) have a high frequency of alterations of genes regulating Ras pathway and cytokine receptor signaling (66.2%; NF1, NRAS, KRAS, PTPN11, FLT3, and PAG1), IKZF3 (encoding the lymphoid transcription factor AIOLOS), and a histone gene cluster at 6p22. Low hypodiploid cases (32-39 chromosomes) are enriched for IKZF2 (HELIOS) and RB1 alterations, but have a low frequency of Ras/signaling alterations. A striking finding was exclusivity of Ras/signaling and IKZF2/3 alterations, and biochemical evidence of Ras pathway activation in... (for more see dbGaP study page.)