@article{1928b15c8f7d45d4be0105793ca18b58,
title = "Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia",
abstract = "There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal diversity is comparable at diagnosis and relapse and clonal survival from diagnosis to relapse is not associated with mutation burden. Six pathways were frequently mutated, with NT5C2, CREBBP, WHSC1, TP53, USH2A, NRAS and IKZF1 mutations enriched at relapse. Half of the leukaemias had multiple subclonal mutations in a pathway or gene at diagnosis, but mostly with only one, usually minor clone, surviving therapy to acquire additional mutations and become the relapse founder clone. Relapse-specific mutations in NT5C2 were found in nine cases, with mutations in four cases being in descendants of the relapse founder clone. These results provide important insights into the genetic basis of treatment failure in ALL and have implications for the early detection of mutations driving relapse.",
author = "Xiaotu Ma and Michael Edmonson and Donald Yergeau and Muzny, {Donna M.} and Hampton, {Oliver A.} and Michael Rusch and Guangchun Song and John Easton and Harvey, {Richard C.} and Wheeler, {David A.} and Jing Ma and Harshavardhan Doddapaneni and Bhavin Vadodaria and Gang Wu and Panduka Nagahawatte and Carroll, {William L.} and Chen, {I. Ming} and Gastier-Foster, {Julie M.} and Relling, {Mary V.} and Smith, {Malcolm A.} and Meenakshi Devidas and Auvil, {Jaime M.Guidry} and Downing, {James R.} and Loh, {Mignon L.} and Willman, {Cheryl L.} and Gerhard, {Daniela S.} and Mullighan, {Charles G.} and Hunger, {Stephen P.} and Jinghui Zhang",
note = "Funding Information: The Acute Lymphoblastic Leukemia (ALL) data set is part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative, supported by a supplement to NCI Grant U10 CA98543 to the Children{\textquoteright}s Oncology Group (COG). This is a collaborative project of the COG, the University of New Mexico Cancer Center, the St Jude{\textquoteright}s Children{\textquoteright}s Research Hospital Pediatric Cancer Genome Project and the National Cancer Institute. This work was supported in part by the American Lebanese Syrian Associated Charities and National Institutes of Health Grants CA21765 and GM92666 to St Jude Children{\textquoteright}s Research Hospital and a St Baldrick{\textquoteright}s Foundation Scholar Award (to C.G.M.), and by grants to the Children{\textquoteright}s Oncology Group U10 CA98543 (Chair{\textquoteright}s grant and supplement to support the COG High-Risk ALL TARGET project), U10 CA98413 (Statistical Center) and U24 CA114766 (Specimen Banking). This project has been funded in part by the Federal ARRA funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views of policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",
year = "2015",
month = mar,
day = "19",
doi = "10.1038/ncomms7604",
language = "English (US)",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}