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Genomic characterization implicates iAMP21 as a likely primary genetic event in childhood B-cell precursor acute lymphoblastic leukemia

Genomic characterization implicates iAMP21 as a likely primary genetic event in childhood B-cell precursor acute lymphoblastic leukemia
Genomic characterization implicates iAMP21 as a likely primary genetic event in childhood B-cell precursor acute lymphoblastic leukemia
Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct subgroup of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) that has a dismal outcome when treated with standard therapy. For improved diagnosis and risk stratification, the initiating genetic events need to be elucidated. To investigate the genetic basis of BCP-ALL, genomes of 94 iAMP21 patients were interrogated by arrays, FISH, and multiplex ligation-dependent probe amplification. Most copy number alterations targeted chromosome 21, reinforcing the complexity of this chromosome. The common region of amplification on chromosome 21 was refined to a 5.1-mb region that included RUNX1, miR-802, and genes mapping to the Down syndrome critical region. Recurrent abnormalities affecting genes in key pathways were identified: IKZF1 (22%), CDKN2A/B (17%), PAX5 (8%), ETV6 (19%), and RB1 (37%). Investigation of clonal architecture provided evidence that these abnormalities, and P2RY8-CRLF2, were secondary to chromosome 21 rearrangements. Patient outcome was uniformly poor with standard therapy irrespective of the presence or absence of these changes. This study has provided evidence that chromosome 21 instability is the only anomaly among those so far investigated that is common to all iAMP21 patients, and therefore the initiating event is likely to be found among the complex structural rearrangements of this abnormal chromosome
0006-4971
6848-55
Rand, Vikki
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Parker, Helen
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Russell, Lisa J
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Schwab, Claire
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Ensor, Hannah
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Irving, Julie
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Jones, Lisa
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Masic, Dino
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Minto, Lynne
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Morrison, Heather
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Ryan, Sarra
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Robinson, Hazel
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Sinclair, Paul
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Moorman, Anthony V
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Strefford, Jonathan C.
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Harrison, Christine J.
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Rand, Vikki
e61c839d-fda5-49e9-a497-e58bfad17934
Parker, Helen
33e0cd81-d45f-49bc-9539-09345d79d895
Russell, Lisa J
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Schwab, Claire
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Ensor, Hannah
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Irving, Julie
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Jones, Lisa
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Masic, Dino
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Minto, Lynne
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Morrison, Heather
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Ryan, Sarra
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Robinson, Hazel
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Sinclair, Paul
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Moorman, Anthony V
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Strefford, Jonathan C.
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Harrison, Christine J.
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Rand, Vikki, Parker, Helen, Russell, Lisa J, Schwab, Claire, Ensor, Hannah, Irving, Julie, Jones, Lisa, Masic, Dino, Minto, Lynne, Morrison, Heather, Ryan, Sarra, Robinson, Hazel, Sinclair, Paul, Moorman, Anthony V, Strefford, Jonathan C. and Harrison, Christine J. (2011) Genomic characterization implicates iAMP21 as a likely primary genetic event in childhood B-cell precursor acute lymphoblastic leukemia. Blood, 117 (25), 6848-55. (doi:10.1182/blood-2011-01-329961). (PMID:21527530)

Record type: Article

Abstract

Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct subgroup of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) that has a dismal outcome when treated with standard therapy. For improved diagnosis and risk stratification, the initiating genetic events need to be elucidated. To investigate the genetic basis of BCP-ALL, genomes of 94 iAMP21 patients were interrogated by arrays, FISH, and multiplex ligation-dependent probe amplification. Most copy number alterations targeted chromosome 21, reinforcing the complexity of this chromosome. The common region of amplification on chromosome 21 was refined to a 5.1-mb region that included RUNX1, miR-802, and genes mapping to the Down syndrome critical region. Recurrent abnormalities affecting genes in key pathways were identified: IKZF1 (22%), CDKN2A/B (17%), PAX5 (8%), ETV6 (19%), and RB1 (37%). Investigation of clonal architecture provided evidence that these abnormalities, and P2RY8-CRLF2, were secondary to chromosome 21 rearrangements. Patient outcome was uniformly poor with standard therapy irrespective of the presence or absence of these changes. This study has provided evidence that chromosome 21 instability is the only anomaly among those so far investigated that is common to all iAMP21 patients, and therefore the initiating event is likely to be found among the complex structural rearrangements of this abnormal chromosome

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Published date: 23 June 2011
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 192019
URI: http://eprints.soton.ac.uk/id/eprint/192019
ISSN: 0006-4971
PURE UUID: c1638047-810d-4a05-8970-f5f8e73e70ce
ORCID for Helen Parker: ORCID iD orcid.org/0000-0001-8308-9781
ORCID for Jonathan C. Strefford: ORCID iD orcid.org/0000-0002-0972-2881

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Date deposited: 29 Jun 2011 07:44
Last modified: 15 Mar 2024 03:20

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Contributors

Author: Vikki Rand
Author: Helen Parker ORCID iD
Author: Lisa J Russell
Author: Claire Schwab
Author: Hannah Ensor
Author: Julie Irving
Author: Lisa Jones
Author: Dino Masic
Author: Lynne Minto
Author: Heather Morrison
Author: Sarra Ryan
Author: Hazel Robinson
Author: Paul Sinclair
Author: Anthony V Moorman
Author: Christine J. Harrison

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