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Characterizing the allele-specific gene expression landscape in high hyperdiploid acute lymphoblastic leukemia with BASE

Andersson, Jonas LU orcid ; Aydin, Efe LU ; Gunnarsson, Rebeqa LU ; Lilljebjörn, Henrik LU orcid ; Fioretos, Thoas LU ; Johansson, Bertil LU ; Paulsson, Kajsa LU and Yang, Minjun LU (2024) In Scientific Reports 14. p.1-10
Abstract
Somatic copy number variations (CNVs), including abnormal chromosome numbers and structural changes leading to gain or loss of genetic material, play a crucial role in initiation and progression of cancer. CNVs are believed to cause gene dosage imbalances and modify cis-regulatory elements, leading to allelic expression imbalances in genes that influence cell division and thereby contribute to cancer development. However, the impact of CNVs on allelic gene expression in cancer remains unclear. Allele-specific expression (ASE) analysis, a potent method for investigating genome-wide allelic imbalance profiles in tumors, assesses the relative expression of two alleles using high-throughput sequencing data. However, many existing methods for... (More)
Somatic copy number variations (CNVs), including abnormal chromosome numbers and structural changes leading to gain or loss of genetic material, play a crucial role in initiation and progression of cancer. CNVs are believed to cause gene dosage imbalances and modify cis-regulatory elements, leading to allelic expression imbalances in genes that influence cell division and thereby contribute to cancer development. However, the impact of CNVs on allelic gene expression in cancer remains unclear. Allele-specific expression (ASE) analysis, a potent method for investigating genome-wide allelic imbalance profiles in tumors, assesses the relative expression of two alleles using high-throughput sequencing data. However, many existing methods for gene-level ASE detection rely on only RNA sequencing data, which present challenges in interpreting the genetic mechanisms underlying ASE in cancer. To address this issue, we developed a robust framework that integrates allele-specific copy number calls into ASE calling algorithms by leveraging paired genome and transcriptome data from the same sample. This integration enhances the interpretability of the genetic mechanisms driving ASE, thereby facilitating the identification of driver events triggered by CNVs in cancer. In this study, we utilized BASE to conduct a comprehensive analysis of ASE in high hyperdiploid acute lymphoblastic leukemia (HeH ALL), a prevalent childhood malignancy characterized by gains of chromosomes X, 4, 6, 10, 14, 17, 18, and 21. Our analysis unveiled the comprehensive ASE landscape in HeH ALL. Through a multi-perspective examination of HeH ASEs, we offer a systematic understanding of how CNVs impact ASE in HeH, providing valuable insights to guide ASE studies in cancer. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Allele-specific gene expression, Aneuploidy
in
Scientific Reports
volume
14
article number
23181
pages
1 - 10
publisher
Nature Publishing Group
external identifiers
  • pmid:39369032
  • scopus:85205771410
ISSN
2045-2322
DOI
10.1038/s41598-024-73743-8
language
English
LU publication?
yes
id
ee86ed98-df8b-4539-971f-15e19074df1c
date added to LUP
2024-10-22 22:04:27
date last changed
2025-04-04 15:05:39
@article{ee86ed98-df8b-4539-971f-15e19074df1c,
  abstract     = {{Somatic copy number variations (CNVs), including abnormal chromosome numbers and structural changes leading to gain or loss of genetic material, play a crucial role in initiation and progression of cancer. CNVs are believed to cause gene dosage imbalances and modify cis-regulatory elements, leading to allelic expression imbalances in genes that influence cell division and thereby contribute to cancer development. However, the impact of CNVs on allelic gene expression in cancer remains unclear. Allele-specific expression (ASE) analysis, a potent method for investigating genome-wide allelic imbalance profiles in tumors, assesses the relative expression of two alleles using high-throughput sequencing data. However, many existing methods for gene-level ASE detection rely on only RNA sequencing data, which present challenges in interpreting the genetic mechanisms underlying ASE in cancer. To address this issue, we developed a robust framework that integrates allele-specific copy number calls into ASE calling algorithms by leveraging paired genome and transcriptome data from the same sample. This integration enhances the interpretability of the genetic mechanisms driving ASE, thereby facilitating the identification of driver events triggered by CNVs in cancer. In this study, we utilized BASE to conduct a comprehensive analysis of ASE in high hyperdiploid acute lymphoblastic leukemia (HeH ALL), a prevalent childhood malignancy characterized by gains of chromosomes X, 4, 6, 10, 14, 17, 18, and 21. Our analysis unveiled the comprehensive ASE landscape in HeH ALL. Through a multi-perspective examination of HeH ASEs, we offer a systematic understanding of how CNVs impact ASE in HeH, providing valuable insights to guide ASE studies in cancer.}},
  author       = {{Andersson, Jonas and Aydin, Efe and Gunnarsson, Rebeqa and Lilljebjörn, Henrik and Fioretos, Thoas and Johansson, Bertil and Paulsson, Kajsa and Yang, Minjun}},
  issn         = {{2045-2322}},
  keywords     = {{Allele-specific gene expression; Aneuploidy}},
  language     = {{eng}},
  month        = {{10}},
  pages        = {{1--10}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Characterizing the allele-specific gene expression landscape in high hyperdiploid acute lymphoblastic leukemia with BASE}},
  url          = {{http://dx.doi.org/10.1038/s41598-024-73743-8}},
  doi          = {{10.1038/s41598-024-73743-8}},
  volume       = {{14}},
  year         = {{2024}},
}