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St. Jude Children''s Research Hospital - Washington University Pediatric Cancer Genome Project(PCGP): Whole genome sequencing of infant acute lymphoblastic leukemia
Infant acute lymphoblastic leukemia (ALL) is characterized by a poor prognosis and a high frequency of rearrangements of the MLL gene at chromosome band 11q23. To gain further insight into the genetic and molecular basis of this disease, we performed whole genome sequencing of tumor and normal DNA samples obtained from 22 infant ALL cases with MLL rearrangements. Analysis of structural and sequence variants revealed that infant ALL has the lowest frequency of mutations of all cancers sequenced within the pediatric cancer genome project to date. Genes involved in Ras signaling were frequently targeted by sequence mutations and included KRAS, NRAS, and PTPN11. In addition, the B-cell regulator PAX5 was found to be mutated or disrupted by copy number gains or losses in several cases. Focal genomic imbalances spanning the genomic break points of the MLL gene and the different MLL partner genes were observed confirming that these seemingly balanced chromosomal... (for more see dbGaP study page.)