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Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

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

Author

  • Jonas Andersson
  • Efe Aydin
  • Rebeqa Gunnarsson
  • Henrik Lilljebjörn
  • Thoas Fioretos
  • Bertil Johansson
  • Kajsa Paulsson
  • Minjun Yang

Summary, in English

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.

Department/s

  • Genetics and Diabetes
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • LUCC: Lund University Cancer Centre
  • Aneuploidy in cancer
  • Genetic and epigenetic studies of pediatric leukemia
  • Translational Genomic and Functional Studies of Leukemia
  • LTH Profile Area: Engineering Health

Publishing year

2024-10-05

Language

English

Pages

1-10

Publication/Series

Scientific Reports

Volume

14

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics
  • Cancer and Oncology

Keywords

  • Allele-specific gene expression
  • Aneuploidy

Status

Published

Research group

  • Aneuploidy in cancer
  • Genetic and epigenetic studies of pediatric leukemia
  • Translational Genomic and Functional Studies of Leukemia

ISBN/ISSN/Other

  • ISSN: 2045-2322