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Mutation, methylation, and gene expression profiles in dup(1q)-positive pediatric B-cell precursor acute lymphoblastic leukemia

Gunnarsson, Rebeqa LU ; Dilorenzo, Sebastian ; Lundin-Ström, Kristina B. LU ; Olsson, Linda LU ; Biloglav, Andrea LU ; Lilljebjörn, Henrik LU ; Rissler, Marianne LU ; Wahlberg, Per ; Lundmark, Anders and Castor, Anders LU , et al. (2018) In Leukemia 32(10). p.2117-2125
Abstract

High-throughput sequencing was applied to investigate the mutation/methylation patterns on 1q and gene expression profiles in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL) with/without (w/wo) dup(1q). Sequencing of the breakpoint regions and all exons on 1q in seven dup(1q)-positive cases revealed non-synonymous somatic single nucleotide variants (SNVs) in BLZF1, FMN2, KCNT2, LCE1C, NES, and PARP1. Deep sequencing of these in a validation cohort w (n = 17)/wo (n = 94) dup(1q) revealed similar SNV frequencies in the two groups (47% vs. 35%; P = 0.42). Only 0.6% of the 36,259 CpGs on 1q were differentially methylated between cases w (n = 14)/wo (n = 13) dup(1q). RNA sequencing of high hyperdiploid (HeH) and... (More)

High-throughput sequencing was applied to investigate the mutation/methylation patterns on 1q and gene expression profiles in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL) with/without (w/wo) dup(1q). Sequencing of the breakpoint regions and all exons on 1q in seven dup(1q)-positive cases revealed non-synonymous somatic single nucleotide variants (SNVs) in BLZF1, FMN2, KCNT2, LCE1C, NES, and PARP1. Deep sequencing of these in a validation cohort w (n = 17)/wo (n = 94) dup(1q) revealed similar SNV frequencies in the two groups (47% vs. 35%; P = 0.42). Only 0.6% of the 36,259 CpGs on 1q were differentially methylated between cases w (n = 14)/wo (n = 13) dup(1q). RNA sequencing of high hyperdiploid (HeH) and t(1;19)(q23;p13)-positive cases w (n = 14)/wo (n = 52) dup(1q) identified 252 and 424 differentially expressed genes, respectively; only seven overlapped. Of the overexpressed genes in the HeH and t(1;19) groups, 23 and 31%, respectively, mapped to 1q; 60-80% of these encode nucleic acid/protein binding factors or proteins with catalytic activity. We conclude that the pathogenetically important consequence of dup(1q) in BCP ALL is a gene-dosage effect, with the deregulated genes differing between genetic subtypes, but involving similar molecular functions, biological processes, and protein classes.

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published
subject
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Leukemia
volume
32
issue
10
pages
2117 - 2125
publisher
Nature Publishing Group
external identifiers
  • pmid:29626196
  • scopus:85045026892
ISSN
0887-6924
DOI
10.1038/s41375-018-0092-2
language
English
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yes
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d015044a-1a16-41b7-accd-5600f55231bb
date added to LUP
2018-04-20 11:49:45
date last changed
2020-02-12 09:25:28
@article{d015044a-1a16-41b7-accd-5600f55231bb,
  abstract     = {<p>High-throughput sequencing was applied to investigate the mutation/methylation patterns on 1q and gene expression profiles in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL) with/without (w/wo) dup(1q). Sequencing of the breakpoint regions and all exons on 1q in seven dup(1q)-positive cases revealed non-synonymous somatic single nucleotide variants (SNVs) in BLZF1, FMN2, KCNT2, LCE1C, NES, and PARP1. Deep sequencing of these in a validation cohort w (n = 17)/wo (n = 94) dup(1q) revealed similar SNV frequencies in the two groups (47% vs. 35%; P = 0.42). Only 0.6% of the 36,259 CpGs on 1q were differentially methylated between cases w (n = 14)/wo (n = 13) dup(1q). RNA sequencing of high hyperdiploid (HeH) and t(1;19)(q23;p13)-positive cases w (n = 14)/wo (n = 52) dup(1q) identified 252 and 424 differentially expressed genes, respectively; only seven overlapped. Of the overexpressed genes in the HeH and t(1;19) groups, 23 and 31%, respectively, mapped to 1q; 60-80% of these encode nucleic acid/protein binding factors or proteins with catalytic activity. We conclude that the pathogenetically important consequence of dup(1q) in BCP ALL is a gene-dosage effect, with the deregulated genes differing between genetic subtypes, but involving similar molecular functions, biological processes, and protein classes.</p>},
  author       = {Gunnarsson, Rebeqa and Dilorenzo, Sebastian and Lundin-Ström, Kristina B. and Olsson, Linda and Biloglav, Andrea and Lilljebjörn, Henrik and Rissler, Marianne and Wahlberg, Per and Lundmark, Anders and Castor, Anders and Behrendtz, Mikael and Fioretos, Thoas and Paulsson, Kajsa and Isaksson, Anders and Johansson, Bertil},
  issn         = {0887-6924},
  language     = {eng},
  month        = {03},
  number       = {10},
  pages        = {2117--2125},
  publisher    = {Nature Publishing Group},
  series       = {Leukemia},
  title        = {Mutation, methylation, and gene expression profiles in dup(1q)-positive pediatric B-cell precursor acute lymphoblastic leukemia},
  url          = {http://dx.doi.org/10.1038/s41375-018-0092-2},
  doi          = {10.1038/s41375-018-0092-2},
  volume       = {32},
  year         = {2018},
}