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DOI 10.1038/s41588-022-01159-z

Медицинская библиотека · Nature genetics · 2022

The genomic landscape of pediatric acute lymphoblastic leukemia.

Brady Samuel W, Roberts Kathryn G, Gu Zhaohui, Shi Lei, Pounds Stanley, Pei Deqing, Cheng Cheng, Dai Yunfeng, Devidas Meenakshi, Qu Chunxu, Hill Ashley N, Payne-Turner Debbie, Ma Xiaotu, Iacobucci Ilaria, Baviskar Pradyuamna, Wei Lei, Arunachalam Sasi, Hagiwara Kohei, Liu Yanling, Flasch Diane A, Liu Yu, Parker Matthew, Chen Xiaolong, Elsayed Abdelrahman H, Pathak Omkar, Li Yongjin, Fan Yiping, Michael J Robert, Rusch Michael, Wilkinson Mark R, Foy Scott, Hedges Dale J, Newman Scott, Zhou Xin, Wang Jian, Reilly Colleen, Sioson Edgar, Rice Stephen V, Pastor Loyola Victor, Wu Gang, Rampersaud Evadnie, Reshmi Shalini C, Gastier-Foster Julie, Guidry Auvil Jaime M, Gesuwan Patee, Smith Malcolm A, Winick Naomi, Carroll Andrew J, Heerema Nyla A, Harvey Richard C, Willman Cheryl L, Larsen Eric, Raetz Elizabeth A, Borowitz Michael J, Wood Brent L, Carroll William L, Zweidler-McKay Patrick A, Rabin Karen R, Mattano Leonard A, Maloney Kelly W, Winter Stuart S, Burke Michael J, Salzer Wanda, Dunsmore Kimberly P, Angiolillo Anne L, Crews Kristine R, Downing James R, Jeha Sima, Pui Ching-Hon, Evans William E, Yang Jun J, Relling Mary V, Gerhard Daniela S, Loh Mignon L, Hunger Stephen P, Zhang Jinghui, Mullighan Charles G

СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаПеревод в очереди

Аннотация

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.

Для цитирования: Brady Samuel W, Roberts Kathryn G, Gu Zhaohui, Shi Lei, Pounds Stanley, Pei Deqing, Cheng Cheng, Dai Yunfeng, Devidas Meenakshi, Qu Chunxu, Hill Ashley N, Payne-Turner Debbie, Ma Xiaotu, Iacobucci Ilaria, Baviskar Pradyuamna, Wei Lei, Arunachalam Sasi, Hagiwara Kohei, Liu Yanling, Flasch Diane A, Liu Yu, Parker Matthew, Chen Xiaolong, Elsayed Abdelrahman H, Pathak Omkar, Li Yongjin, Fan Yiping, Michael J Robert, Rusch Michael, Wilkinson Mark R, Foy Scott, Hedges Dale J, Newman Scott, Zhou Xin, Wang Jian, Reilly Colleen, Sioson Edgar, Rice Stephen V, Pastor Loyola Victor, Wu Gang, Rampersaud Evadnie, Reshmi Shalini C, Gastier-Foster Julie, Guidry Auvil Jaime M, Gesuwan Patee, Smith Malcolm A, Winick Naomi, Carroll Andrew J, Heerema Nyla A, Harvey Richard C, Willman Cheryl L, Larsen Eric, Raetz Elizabeth A, Borowitz Michael J, Wood Brent L, Carroll William L, Zweidler-McKay Patrick A, Rabin Karen R, Mattano Leonard A, Maloney Kelly W, Winter Stuart S, Burke Michael J, Salzer Wanda, Dunsmore Kimberly P, Angiolillo Anne L, Crews Kristine R, Downing James R, Jeha Sima, Pui Ching-Hon, Evans William E, Yang Jun J, Relling Mary V, Gerhard Daniela S, Loh Mignon L, Hunger Stephen P, Zhang Jinghui, Mullighan Charles G. The genomic landscape of pediatric acute lymphoblastic leukemia.. Nature genetics. 2022. DOI: 10.1038/s41588-022-01159-z.

Предметные рубрики MeSH

ChildChromosome AberrationsExomeGenomicsHumansMutationPrecursor Cell Lymphoblastic Leukemia-Lymphoma
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