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Comprehensive genetic characterization of pediatric T-cell acute lymphoblastic leukemia

Karrman, Kristina LU ; Castor, Anders LU ; Behrendtz, Mikael; Forestier, Erik; Olsson, Linda LU ; Ehinger, Mats LU ; Biloglav, Andrea LU ; Fioretos, Thoas LU ; Paulsson, Kajsa LU and Johansson, Bertil LU (2014) 56th Annual Meeting of the American Society of Hematology In Blood 124(21). p.1084-1084
Abstract
A comprehensive genetic characterization comprising conventional chromosome banding, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism (SNP) array analyses as well as large-scale sequencing of 75 genes were performed on a consecutive series of 47 pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients. An abnormal karyotype was identified in 46% of the cases. Recurrent cytogenetic aberrations comprised T-cell receptor (TCR) translocations and deletions of 6q and 9p. FISH analyses of TCR rearrangements were positive in 26% of the investigated cases. The vast majority (37/39; 95%) of cases analyzed by SNP arrays displayed aberrations, with a median of 3 changes (range 0-11) per case. The genes recurrently... (More)
A comprehensive genetic characterization comprising conventional chromosome banding, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism (SNP) array analyses as well as large-scale sequencing of 75 genes were performed on a consecutive series of 47 pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients. An abnormal karyotype was identified in 46% of the cases. Recurrent cytogenetic aberrations comprised T-cell receptor (TCR) translocations and deletions of 6q and 9p. FISH analyses of TCR rearrangements were positive in 26% of the investigated cases. The vast majority (37/39; 95%) of cases analyzed by SNP arrays displayed aberrations, with a median of 3 changes (range 0-11) per case. The genes recurrently deleted were CDKN2A, CDKN2B, LEF1, PTEN, RBI, and STIL. One case displayed chromothripsis involving 6q. No case had a whole chromosome uniparental isodisomy (wUPID); in fact, only one T-ALL of 123 informative cases in the literature has had a wUPID. However, segmental UPIDs (sUPIDs) were seen in 44% of the present cases, with most being sUPID9p. CDKN2A was homozygously deleted in all cases with sUPID9p, with a heterozygous deletion occurring prior to the sUPID9p in all instances. There was no evidence for chromosomal instability when comparing diagnostic and relapse samples. Among the genes sequenced, 14 were mutated in 28 cases. The genes targeted are involved in signaling transduction, epigenetic regulation, and transcription. In some cases, NOTCH1 mutations were seen in minor subclones and lost at relapse, showing that such mutations also can be secondary events. These findings support a multistep leukemogenic process. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
T lymphocyte receptor, T lymphocyte, acute lymphoblastic leukemia, American, society, hematology, gene, mutation, relapse, chromosome, chromosome aberration, human, patient, single nucleotide polymorphism, fluorescence in situ hybridization, diagnosis, chromosomal instability, uniparental disomy, chromosome banding pattern
in
Blood
volume
124
issue
21
pages
1084 - 1084
publisher
American Society of Hematology
conference name
56th Annual Meeting of the American Society of Hematology
ISSN
1528-0020
language
English
LU publication?
yes
id
9a2db845-1024-4d8a-a0ee-36ef5d5bf279
date added to LUP
2017-09-10 22:03:42
date last changed
2017-09-11 12:31:11
@misc{9a2db845-1024-4d8a-a0ee-36ef5d5bf279,
  abstract     = {A comprehensive genetic characterization comprising conventional chromosome banding, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism (SNP) array analyses as well as large-scale sequencing of 75 genes were performed on a consecutive series of 47 pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients. An abnormal karyotype was identified in 46% of the cases. Recurrent cytogenetic aberrations comprised T-cell receptor (TCR) translocations and deletions of 6q and 9p. FISH analyses of TCR rearrangements were positive in 26% of the investigated cases. The vast majority (37/39; 95%) of cases analyzed by SNP arrays displayed aberrations, with a median of 3 changes (range 0-11) per case. The genes recurrently deleted were CDKN2A, CDKN2B, LEF1, PTEN, RBI, and STIL. One case displayed chromothripsis involving 6q. No case had a whole chromosome uniparental isodisomy (wUPID); in fact, only one T-ALL of 123 informative cases in the literature has had a wUPID. However, segmental UPIDs (sUPIDs) were seen in 44% of the present cases, with most being sUPID9p. CDKN2A was homozygously deleted in all cases with sUPID9p, with a heterozygous deletion occurring prior to the sUPID9p in all instances. There was no evidence for chromosomal instability when comparing diagnostic and relapse samples. Among the genes sequenced, 14 were mutated in 28 cases. The genes targeted are involved in signaling transduction, epigenetic regulation, and transcription. In some cases, NOTCH1 mutations were seen in minor subclones and lost at relapse, showing that such mutations also can be secondary events. These findings support a multistep leukemogenic process.},
  author       = {Karrman, Kristina and Castor, Anders and Behrendtz, Mikael and Forestier, Erik and Olsson, Linda and Ehinger, Mats and Biloglav, Andrea and Fioretos, Thoas and Paulsson, Kajsa and Johansson, Bertil},
  issn         = {1528-0020},
  keyword      = {T lymphocyte receptor,T lymphocyte,acute lymphoblastic leukemia,American,society,hematology,gene,mutation,relapse,chromosome,chromosome aberration,human,patient,single nucleotide polymorphism,fluorescence in situ hybridization,diagnosis,chromosomal instability,uniparental disomy,chromosome banding pattern},
  language     = {eng},
  month        = {12},
  note         = {Conference Abstract},
  number       = {21},
  pages        = {1084--1084},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Comprehensive genetic characterization of pediatric T-cell acute lymphoblastic leukemia},
  volume       = {124},
  year         = {2014},
}