| Literature DB >> 36050548 |
Samuel W Brady1, Kathryn G Roberts2, Zhaohui Gu3, Lei Shi4, Stanley Pounds4, Deqing Pei4, Cheng Cheng4, Yunfeng Dai5, Meenakshi Devidas6, Chunxu Qu2, Ashley N Hill2, Debbie Payne-Turner2, Xiaotu Ma1, Ilaria Iacobucci2, Pradyuamna Baviskar2, Lei Wei1, Sasi Arunachalam1, Kohei Hagiwara1, Yanling Liu1, Diane A Flasch1, Yu Liu1, Matthew Parker1, Xiaolong Chen1, Abdelrahman H Elsayed2,4, Omkar Pathak1, Yongjin Li1, Yiping Fan1, J Robert Michael1, Michael Rusch1, Mark R Wilkinson1, Scott Foy1, Dale J Hedges1, Scott Newman1, Xin Zhou1, Jian Wang1, Colleen Reilly1, Edgar Sioson1, Stephen V Rice1, Victor Pastor Loyola1, Gang Wu7, Evadnie Rampersaud7, Shalini C Reshmi8, Julie Gastier-Foster9, Jaime M Guidry Auvil10,11, Patee Gesuwan10, Malcolm A Smith12, Naomi Winick13, Andrew J Carroll14, Nyla A Heerema15, Richard C Harvey16, Cheryl L Willman17, Eric Larsen18, Elizabeth A Raetz19, Michael J Borowitz20, Brent L Wood21, William L Carroll19, Patrick A Zweidler-McKay22, Karen R Rabin9, Leonard A Mattano23, Kelly W Maloney24, Stuart S Winter25, Michael J Burke26, Wanda Salzer27, Kimberly P Dunsmore28, Anne L Angiolillo29, Kristine R Crews30, James R Downing2, Sima Jeha31, Ching-Hon Pui31, William E Evans30, Jun J Yang30, Mary V Relling30, Daniela S Gerhard10, Mignon L Loh32, Stephen P Hunger33, Jinghui Zhang34, Charles G Mullighan35.
Abstract
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Here, using whole-genome, exome and transcriptome sequencing of 2,754 childhood patients with ALL, we find that, despite a generally low mutation burden, ALL cases harbor a median of four putative somatic driver alterations per sample, with 376 putative driver genes identified varying in prevalence across ALL subtypes. Most samples harbor at least one rare gene alteration, including 70 putative cancer driver genes associated with ubiquitination, SUMOylation, noncoding transcripts and other functions. In hyperdiploid B-ALL, chromosomal gains are acquired early and synchronously before ultraviolet-induced mutation. By contrast, ultraviolet-induced mutations precede chromosomal gains in B-ALL cases with intrachromosomal amplification of chromosome 21. We also demonstrate the prognostic significance of genetic alterations within subtypes. Intriguingly, DUX4- and KMT2A-rearranged subtypes separate into CEBPA/FLT3- or NFATC4-expressing subgroups with potential clinical implications. Together, these results deepen understanding of the ALL genomic landscape and associated outcomes.Entities:
Mesh：
Year: 2022 PMID： 36050548 DOI： 10.1038/s41588-022-01159-z
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 41.307