Advanced

Patterns and Frequencies of Acquired and Constitutional Uniparental Isodisomies in Pediatric and Adult B-Cell Precursor Acute Lymphoblastic Leukemia.

Lundin, Kristina LU ; Olsson, Linda LU ; Safavi, Setareh LU ; Biloglav, Andrea LU ; Paulsson, Kajsa LU and Johansson, Bertil LU (2016) In Genes, Chromosomes and Cancer 55(5). p.472-479
Abstract
Single nucleotide polymorphism (SNP) arrays are increasingly being used in clinical routine for genetic analysis of pediatric B-cell precursor acute lymphoblastic leukemias (BCP ALL). Because constitutional DNA is not readily available as a control at the time of diagnosis, it is important to be able to distinguish between acquired and constitutional aberrations in a diagnostic setting. In the present study we focused on uniparental isodisomies (UPIDs). SNP array analyses of 143 pediatric and 38 adult B-cell precursor acute lymphoblastic leukemias and matched remission samples revealed acquired whole chromosome or segmental UPIDs (wUPIDs, sUPIDs) in 32 cases (18%), without any age- or gender-related frequency differences. Acquired sUPIDs... (More)
Single nucleotide polymorphism (SNP) arrays are increasingly being used in clinical routine for genetic analysis of pediatric B-cell precursor acute lymphoblastic leukemias (BCP ALL). Because constitutional DNA is not readily available as a control at the time of diagnosis, it is important to be able to distinguish between acquired and constitutional aberrations in a diagnostic setting. In the present study we focused on uniparental isodisomies (UPIDs). SNP array analyses of 143 pediatric and 38 adult B-cell precursor acute lymphoblastic leukemias and matched remission samples revealed acquired whole chromosome or segmental UPIDs (wUPIDs, sUPIDs) in 32 cases (18%), without any age- or gender-related frequency differences. Acquired sUPIDs were larger than the constitutional ones (mean 35.3 Mb vs. 10.7 Mb; P<0.0001) and were more often terminally located in the chromosomes (69% vs. 4.5%; P<0.0001). Chromosomes 3, 5, and 9 were most often involved in acquired wUPIDs, whilst recurrent acquired sUPIDs targeted 6p, 9p, 9q, and 14q. The majority (56%) of sUPID9p was associated with homozygous CDKN2A deletions. In pediatric ALL, all wUPIDs were found in high hyperdiploid (51-67 chromosomes) cases and an extended analysis, also including unmatched diagnostic samples, revealed a higher frequency of wUPID-positivity in higher modal number (56-67 chromosomes) than in lower modal number (51-55 chromosomes) high hyperdiploid cases (34% versus 11%; P=0.04), suggesting different underlying mechanisms of formation of these subtypes of high hyperdiploidy. This article is protected by copyright. All rights reserved. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
55
issue
5
pages
472 - 479
publisher
John Wiley & Sons
external identifiers
  • pmid:26773847
  • scopus:84957674346
  • wos:000372913800007
ISSN
1045-2257
DOI
10.1002/gcc.22349
language
English
LU publication?
yes
id
55cb51b9-00af-4156-a9a3-1cf67c8b7f94 (old id 8577540)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26773847?dopt=Abstract
date added to LUP
2016-02-03 17:14:35
date last changed
2017-11-05 04:41:07
@article{55cb51b9-00af-4156-a9a3-1cf67c8b7f94,
  abstract     = {Single nucleotide polymorphism (SNP) arrays are increasingly being used in clinical routine for genetic analysis of pediatric B-cell precursor acute lymphoblastic leukemias (BCP ALL). Because constitutional DNA is not readily available as a control at the time of diagnosis, it is important to be able to distinguish between acquired and constitutional aberrations in a diagnostic setting. In the present study we focused on uniparental isodisomies (UPIDs). SNP array analyses of 143 pediatric and 38 adult B-cell precursor acute lymphoblastic leukemias and matched remission samples revealed acquired whole chromosome or segmental UPIDs (wUPIDs, sUPIDs) in 32 cases (18%), without any age- or gender-related frequency differences. Acquired sUPIDs were larger than the constitutional ones (mean 35.3 Mb vs. 10.7 Mb; P&lt;0.0001) and were more often terminally located in the chromosomes (69% vs. 4.5%; P&lt;0.0001). Chromosomes 3, 5, and 9 were most often involved in acquired wUPIDs, whilst recurrent acquired sUPIDs targeted 6p, 9p, 9q, and 14q. The majority (56%) of sUPID9p was associated with homozygous CDKN2A deletions. In pediatric ALL, all wUPIDs were found in high hyperdiploid (51-67 chromosomes) cases and an extended analysis, also including unmatched diagnostic samples, revealed a higher frequency of wUPID-positivity in higher modal number (56-67 chromosomes) than in lower modal number (51-55 chromosomes) high hyperdiploid cases (34% versus 11%; P=0.04), suggesting different underlying mechanisms of formation of these subtypes of high hyperdiploidy. This article is protected by copyright. All rights reserved.},
  author       = {Lundin, Kristina and Olsson, Linda and Safavi, Setareh and Biloglav, Andrea and Paulsson, Kajsa and Johansson, Bertil},
  issn         = {1045-2257},
  language     = {eng},
  month        = {01},
  number       = {5},
  pages        = {472--479},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Patterns and Frequencies of Acquired and Constitutional Uniparental Isodisomies in Pediatric and Adult B-Cell Precursor Acute Lymphoblastic Leukemia.},
  url          = {http://dx.doi.org/10.1002/gcc.22349},
  volume       = {55},
  year         = {2016},
}