Acquisition of genome-wide copy number alterations in monozygotic twins with acute lymphoblastic leukemia.

2.50
Hdl Handle:
http://hdl.handle.net/10541/109480
Title:
Acquisition of genome-wide copy number alterations in monozygotic twins with acute lymphoblastic leukemia.
Authors:
Bateman, Caroline M; Colman, 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
Abstract:
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.
Affiliation:
Section of Haemato-Oncology, The Institute of Cancer Research, Surrey, UK.
Citation:
Acquisition of genome-wide copy number alterations in monozygotic twins with acute lymphoblastic leukemia. 2010, 115 (17):3553-8 Blood
Journal:
Blood
Issue Date:
29-Apr-2010
URI:
http://hdl.handle.net/10541/109480
DOI:
10.1182/blood-2009-10-251413
PubMed ID:
20061556
Type:
Article
Language:
en
ISSN:
1528-0020
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorBateman, Caroline Men
dc.contributor.authorColman, Susan Men
dc.contributor.authorChaplin, Tracyen
dc.contributor.authorYoung, Bryan Den
dc.contributor.authorEden, Tim O Ben
dc.contributor.authorBhakta, Manooen
dc.contributor.authorGratias, Eric Jen
dc.contributor.authorvan Wering, Elisabeth Ren
dc.contributor.authorCazzaniga, Giovannien
dc.contributor.authorHarrison, Christine Jen
dc.contributor.authorHain, Richarden
dc.contributor.authorAncliff, Philipen
dc.contributor.authorFord, Anthony Men
dc.contributor.authorKearney, Lyndalen
dc.contributor.authorGreaves, Mel Fen
dc.date.accessioned2010-08-11T11:01:38Z-
dc.date.available2010-08-11T11:01:38Z-
dc.date.issued2010-04-29-
dc.identifier.citationAcquisition of genome-wide copy number alterations in monozygotic twins with acute lymphoblastic leukemia. 2010, 115 (17):3553-8 Blooden
dc.identifier.issn1528-0020-
dc.identifier.pmid20061556-
dc.identifier.doi10.1182/blood-2009-10-251413-
dc.identifier.urihttp://hdl.handle.net/10541/109480-
dc.description.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.en
dc.language.isoenen
dc.subjectPrecursor Cell Lymphoblastic Leukaemia-Lymphomaen
dc.subject.meshCore Binding Factor Alpha 2 Subunit-
dc.subject.meshFemale-
dc.subject.meshGene Dosage-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMutation-
dc.subject.meshOligonucleotide Array Sequence Analysis-
dc.subject.meshOncogene Proteins, Fusion-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphoma-
dc.subject.meshTwins, Monozygotic-
dc.titleAcquisition of genome-wide copy number alterations in monozygotic twins with acute lymphoblastic leukemia.en
dc.typeArticleen
dc.contributor.departmentSection of Haemato-Oncology, The Institute of Cancer Research, Surrey, UK.en
dc.identifier.journalBlooden
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