Author
Listed:
- Xiaotu Ma
(Computational Biology, St Jude Children’s Research Hospital)
- Michael Edmonson
(Computational Biology, St Jude Children’s Research Hospital)
- Donald Yergeau
(Pediatric Cancer Genome Project Validation Lab, St Jude Children’s Research Hospital)
- Donna M. Muzny
(Cancer Genomics, Human Genome Sequencing Center, Baylor College of Medicine)
- Oliver A. Hampton
(Cancer Genomics, Human Genome Sequencing Center, Baylor College of Medicine)
- Michael Rusch
(Computational Biology, St Jude Children’s Research Hospital)
- Guangchun Song
(Pathology, St Jude Children’s Research Hospital)
- John Easton
(Pediatric Cancer Genome Project Validation Lab, St Jude Children’s Research Hospital)
- Richard C. Harvey
(University of New Mexico Cancer Center)
- David A. Wheeler
(Cancer Genomics, Human Genome Sequencing Center, Baylor College of Medicine)
- Jing Ma
(Pathology, St Jude Children’s Research Hospital)
- HarshaVardhan Doddapaneni
(Cancer Genomics, Human Genome Sequencing Center, Baylor College of Medicine)
- Bhavin Vadodaria
(Pediatric Cancer Genome Project Validation Lab, St Jude Children’s Research Hospital)
- Gang Wu
(Computational Biology, St Jude Children’s Research Hospital)
- Panduka Nagahawatte
(Computational Biology, St Jude Children’s Research Hospital)
- William L. Carroll
(Perlmutter Cancer Center, NYU Langone Medical Center)
- I-Ming Chen
(University of New Mexico Cancer Center)
- Julie M. Gastier-Foster
(Nationwide Children's Hospital
The Ohio State University)
- Mary V. Relling
(St Jude Children’s Research Hospital)
- Malcolm A. Smith
(Cancer Therapy Evaluation Program, National Cancer Institute)
- Meenakshi Devidas
(Colleges of Medicine, Public Health & Health Professions, University of Florida)
- Jaime M. Guidry Auvil
(Office of Cancer Genomics, National Cancer Institute)
- James R. Downing
(Pathology, St Jude Children’s Research Hospital)
- Mignon L. Loh
(Benioff Children’s Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California San Francisco)
- Cheryl L. Willman
(University of New Mexico Cancer Center)
- Daniela S. Gerhard
(Office of Cancer Genomics, National Cancer Institute)
- Charles G. Mullighan
(Pathology, St Jude Children’s Research Hospital)
- Stephen P. Hunger
(Children’s Hospital of Philadelphia)
- Jinghui Zhang
(Computational Biology, St Jude Children’s Research Hospital)
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.
Suggested Citation
Xiaotu Ma & Michael Edmonson & Donald Yergeau & Donna M. Muzny & Oliver A. Hampton & Michael Rusch & Guangchun Song & John Easton & Richard C. Harvey & David A. Wheeler & Jing Ma & HarshaVardhan Dodda, 2015.
"Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia,"
Nature Communications, Nature, vol. 6(1), pages 1-12, May.
Handle:
RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7604
DOI: 10.1038/ncomms7604
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Citations
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Cited by:
- Ting Liu & Jianan Rao & Wenting Hu & Bowen Cui & Jiaoyang Cai & Yuhan Liu & Huiying Sun & Xiaoxiao Chen & Yanjing Tang & Jing Chen & Xiang Wang & Han Wang & Wubin Qian & Binchen Mao & Sheng Guo & Rong, 2022.
"Distinct genomic landscape of Chinese pediatric acute myeloid leukemia impacts clinical risk classification,"
Nature Communications, Nature, vol. 13(1), pages 1-11, December.
- Amanda C. Lorentzian & Jenna Rever & Enes K. Ergin & Meiyun Guo & Neha M. Akella & Nina Rolf & C. James Lim & Gregor S. D. Reid & Christopher A. Maxwell & Philipp F. Lange, 2023.
"Targetable lesions and proteomes predict therapy sensitivity through disease evolution in pediatric acute lymphoblastic leukemia,"
Nature Communications, Nature, vol. 14(1), pages 1-14, December.
- Dominik Beck & Honghui Cao & Feng Tian & Yizhou Huang & Miao Jiang & Han Zhao & Xiaolu Tai & Wenqian Xu & Hansen J. Kosasih & David J. Kealy & Weiye Zhao & Samuel J. Taylor & Timothy A. Couttas & Gaox, 2024.
"PU.1 eviction at lymphocyte-specific chromatin domains mediates glucocorticoid response in acute lymphoblastic leukemia,"
Nature Communications, Nature, vol. 15(1), pages 1-19, December.
- Yanling Liu & Jonathon Klein & Richa Bajpai & Li Dong & Quang Tran & Pandurang Kolekar & Jenny L. Smith & Rhonda E. Ries & Benjamin J. Huang & Yi-Cheng Wang & Todd A. Alonzo & Liqing Tian & Heather L., 2023.
"Etiology of oncogenic fusions in 5,190 childhood cancers and its clinical and therapeutic implication,"
Nature Communications, Nature, vol. 14(1), pages 1-18, December.
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