Acquisition of genome-wide copy number alterations in monozygotic twins with acute lymphoblastic leukemia.
AuthorsBateman, Caroline M
Colman, Susan M
Young, Bryan D
Eden, Tim O B
Gratias, Eric J
van Wering, Elisabeth R
Harrison, Christine J
Ford, Anthony M
Greaves, Mel F
AffiliationSection of Haemato-Oncology, The Institute of Cancer Research, Surrey, UK.
MetadataShow full item record
AbstractChimeric fusion genes are highly prevalent in childhood acute lymphoblastic leukemia (ALL) and are mostly prenatal, early genetic events in the evolutionary trajectory of this cancer. ETV6-RUNX1-positive ALL also has multiple ( approximately 6 per case) copy number alterations (CNAs) as revealed by genome-wide single-nucleotide polymorphism arrays. Recurrent CNAs are probably "driver" events contributing critically to clonal diversification and selection, but at diagnosis, their developmental timing is "buried" in the leukemia's covert natural history. This conundrum can be resolved with twin pairs. We identified and compared CNAs in 5 pairs of monozygotic twins with concordant ETV6-RUNX1-positive ALL and 1 pair discordant for ETV6-RUNX1 positive ALL. We compared, within each pair, CNAs classified as potential "driver" or "passenger" mutations based upon recurrency and, where known, gene function. An average of 5.1 (range 3-11) CNAs (excluding immunoglobulin/T-cell receptor alterations) were identified per case. All "driver" CNAs (total of 32) were distinct within each of the 5 twin pairs with concordant ALL. "Driver" CNAs in another twin with ALL were all absent in the shared ETV6-RUNX1-positive preleukemic clone of her healthy co-twin. These data place all "driver" CNAs secondary to the prenatal gene fusion event and most probably postnatal in the sequential, molecular pathogenesis of ALL.
CitationAcquisition of genome-wide copy number alterations in monozygotic twins with acute lymphoblastic leukemia. 2010, 115 (17):3553-8 Blood
- ETV6-RUNX1 fusion gene and additional genetic changes in infant leukemia: a genome-wide analysis.
- Authors: Emerenciano M, Bungaro S, Cazzaniga G, Dorea MD, Coser VM, Magalhães IQ, Biondi A, Pombo-de-Oliveira MS
- Issue date: 2009 Sep
- Clonal origins of ETV6-RUNX1⁺ acute lymphoblastic leukemia: studies in monozygotic twins.
- Authors: Alpar D, Wren D, Ermini L, Mansur MB, van Delft FW, Bateman CM, Titley I, Kearney L, Szczepanski T, Gonzalez D, Ford AM, Potter NE, Greaves M
- Issue date: 2015 Apr
- Genome-wide analysis of cytogenetic aberrations in ETV6/RUNX1-positive childhood acute lymphoblastic leukaemia.
- Authors: Borst L, Wesolowska A, Joshi T, Borup R, Nielsen FC, Andersen MK, Jonsson OG, Wehner PS, Wesenberg F, Frost BM, Gupta R, Schmiegelow K
- Issue date: 2012 May
- The correlation pattern of acquired copy number changes in 164 ETV6/RUNX1-positive childhood acute lymphoblastic leukemias.
- Authors: Lilljebjörn H, Soneson C, Andersson A, Heldrup J, Behrendtz M, Kawamata N, Ogawa S, Koeffler HP, Mitelman F, Johansson B, Fontes M, Fioretos T
- Issue date: 2010 Aug 15
- Genetic abnormalities involved in t(12;21) TEL-AML1 acute lymphoblastic leukemia: analysis by means of array-based comparative genomic hybridization.
- Authors: Tsuzuki S, Karnan S, Horibe K, Matsumoto K, Kato K, Inukai T, Goi K, Sugita K, Nakazawa S, Kasugai Y, Ueda R, Seto M
- Issue date: 2007 May