Acquisition of genome-wide copy number alterations in monozygotic twins with acute lymphoblastic leukemia.
Authors
Bateman, Caroline MColman, Susan M
Chaplin, Tracy
Young, Bryan D
Eden, Tim O B
Bhakta, Manoo
Gratias, Eric J
van Wering, Elisabeth R
Cazzaniga, Giovanni
Harrison, Christine J
Hain, Richard
Ancliff, Philip
Ford, Anthony M
Kearney, Lyndal
Greaves, Mel F
Affiliation
Section of Haemato-Oncology, The Institute of Cancer Research, Surrey, UK.Issue Date
2010-04-29
Metadata
Show full item recordAbstract
Chimeric 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.Citation
Acquisition of genome-wide copy number alterations in monozygotic twins with acute lymphoblastic leukemia. 2010, 115 (17):3553-8 BloodJournal
BloodDOI
10.1182/blood-2009-10-251413PubMed ID
20061556Type
ArticleLanguage
enISSN
1528-0020ae974a485f413a2113503eed53cd6c53
10.1182/blood-2009-10-251413