ArticleNature2014
Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
154 citing papers in PubMed, 284 citations in OpenAlex.
- A genomic and epigenomic lens into the biology of acute lymphoblastic leukaemia.Nature reviews. Cancer · 2026Review
- Telomere Crisis Shapes Cancer Evolution.Cold Spring Harbor perspectives in biology · 2026Review
- A breakage-replication/fusion process explains complex rearrangements and segmental DNA amplification.Nature genetics · 2026Article
- Chromosomal tethering and mitotic transcription promote ecDNA nuclear inheritance.Molecular cell · 2025Article
- Application of Optical Genome Mapping for the Diagnosis and Risk Stratification of Myeloid and Lymphoid Malignancies.International journal of molecular sciences · 2025Article
- Telomere function and regulation from mouse models to human ageing and disease.Nature reviews. Molecular cell biology · 2025Review
- Review
- Chromothripsis in cancer.Nature reviews. Cancer · 2025Review
- Mapping the chromothripsis landscape in urothelial carcinoma unravels great intratumoral and intertumoral heterogeneity.iScience · 2025Article
- Atypical B-Cell Acute Lymphoblastic Leukemia with iAMP21 in the Context of Constitutional Ring Chromosome 21: A Case Report and Review of the Genetic Insights.International journal of molecular sciences · 2025Review
- Chromoanagenesis in Multiple Myeloma: A Comprehensive Overview.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Secondary lesions and sensitivity to signaling inhibitors in iAMP21 acute lymphoblastic leukemia.HemaSphere · 2025Article
- Genetic hallmarks and clinical implications of chromothripsis in childhood T-cell acute lymphoblastic leukemia.Leukemia · 2024Article
- Chromothripsis in myeloid malignancies.Annals of hematology · 2024Review
- Chromothripsis: an emerging crossroad from aberrant mitosis to therapeutic opportunities.Journal of molecular cell biology · 2024Review
- HYENA detects oncogenes activated by distal enhancers in cancer.Nucleic acids research · 2024Article
- Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer.International journal of molecular sciences · 2024Review
- Acute lymphoblastic leukaemia.Nature reviews. Disease primers · 2024Review
- HYENA detects oncogenes activated by distal enhancers in cancer.bioRxiv : the preprint server for biology · 2024Article
- The two sides of chromosomal instability: drivers and brakes in cancer.Signal transduction and targeted therapy · 2024Review
94 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
33 authors at 14 institutions in 6 countries.
Funding
Abstract
Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.