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Åke Borg

Åke Borg

Principal investigator

Åke Borg

Multiregion whole-exome sequencing uncovers the genetic evolution and mutational heterogeneity of early-stage metastatic melanoma


  • Katja Harbst
  • Martin Lauss
  • Helena Cirenajwis
  • Karolin Isaksson
  • Frida Rosengren
  • Therese Törngren
  • Anders Kvist
  • Maria C. Johansson
  • Johan Vallon-Christersson
  • Bo Baldetorp
  • Åke Borg
  • Håkan Olsson
  • Christian Ingvar
  • Ana Carneiro
  • Göran B Jönsson

Summary, in English

Cancer genome sequencing has shed light on the underlying genetic aberrations that drive tumorigenesis. However, current sequencing-based strategies, which focus on a single tumor biopsy, fail to take into account intratumoral heterogeneity. To address this challenge and elucidate the evolutionary history of melanoma, we performed whole-exome and transcriptome sequencing of 41 multiple melanoma biopsies from eight individual tumors. This approach revealed heterogeneous somatic mutations in the range of 3%-38% in individual tumors. Known mutations in melanoma drivers BRAF and NRAS were always ubiquitous events. Using RNA sequencing, we found that the majority of mutations were not expressed or were expressed at very low levels, and preferential expression of a particular mutated allele did not occur frequently. In addition, we found that the proportion of ultraviolet B (UVB) radiation-induced C>T transitions differed significantly (P <0.001) between early and late mutation acquisition, suggesting that different mutational processes operate during the evolution of metastatic melanoma. Finally, clinical history reports revealed that patients harboring a high degree of mutational heterogeneity were associated with more aggressive disease progression. In conclusion, our multiregion tumor-sequencing approach highlights the genetic evolution and non-UVB mutational signatures associated with melanoma development and progression, and may provide a more comprehensive perspective of patient outcome.


  • EpiHealth: Epidemiology for Health
  • Breastcancer-genetics
  • Surgery (Lund)
  • Melanoma Genomics
  • Tumor microenvironment
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year







Cancer Research





Document type

Journal article


American Association for Cancer Research Inc.


  • Cancer and Oncology



Research group

  • Melanoma Genomics


  • ISSN: 0008-5472