GRCh38 · COSMIC v98


This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia.
Paper ID
Liu Y, Easton J, Shao Y, Maciaszek J, Wang Z, Wilkinson MR, McCastlain K, Edmonson M, Pounds SB, Shi L, Zhou X, Ma X, Sioson E, Li Y, Rusch M, Gupta P, Pei D, Cheng C, Smith MA, Auvil JG, Gerhard DS, Relling MV, Winick NJ, Carroll AJ, Heerema NA, Raetz E, Devidas M, Willman CL, Harvey RC, Carroll WL, Dunsmore KP, Winter SS, Wood BL, Sorrentino BP, Downing JR, Loh ML, Hunger SP, Zhang J and Mullighan CG
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Nature genetics, 2017
ISSN: 1546-1718
PMID: 28671688 (view at PubMed or Europe PMC)
Genetic alterations that activate NOTCH1 signaling and T cell transcription factors, coupled with inactivation of the INK4/ARF tumor suppressors, are hallmarks of T-lineage acute lymphoblastic leukemia (T-ALL), but detailed genome-wide sequencing of large T-ALL cohorts has not been carried out. Using integrated genomic analysis of 264 T-ALL cases, we identified 106 putative driver genes, half of which had not previously been described in childhood T-ALL (for example, CCND3, CTCF, MYB, SMARCA4, ZFP36L2 and MYCN). We describe new mechanisms of coding and noncoding alteration and identify ten recurrently altered pathways, with associations between mutated genes and pathways, and stage or subtype of T-ALL. For example, NRAS/FLT3 mutations were associated with immature T-ALL, JAK3/STAT5B mutations in HOXA1 deregulated ALL, PTPN2 mutations in TLX1 deregulated T-ALL, and PIK3R1/PTEN mutations in TAL1 deregulated ALL, which suggests that different signaling pathways have distinct roles according to maturational stage. This genomic landscape provides a logical framework for the development of faithful genetic models and new therapeutic approaches.
Paper Status