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Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

DNA promoter hypermethylation of melanocyte lineage genes determines melanoma phenotype

Author

  • Adriana Sanna
  • Bengt Phung
  • Shamik Mitra
  • Martin Lauss
  • Jiyeon Choi
  • Tongwu Zhang
  • Ching-Ni Jenny Njauw
  • Eugenia Cordero
  • Katja Harbst
  • Frida Rosengren
  • Rita Cabrita
  • Iva Johansson
  • Karolin Isaksson
  • Christian Ingvar
  • Ana Carneiro
  • Kevin Brown
  • Hensin Tsao
  • My Andersson
  • Kristian Pietras
  • Göran Jönsson
Show all

Summary, in English

Cellular stress contributes to the capacity of melanoma cells to undergo phenotype switching into highly migratory and drug tolerant dedifferentiated states. Such dedifferentiated melanoma cell states are marked by loss of melanocyte specific gene expression and increase of mesenchymal markers. Two crucial transcription factors, MITF and SOX10, important in melanoma development and progression have been implicated in this process. In this study we describe that loss of MITF is associated with a distinct transcriptional program, MITF promoter hypermethylation and poor patient survival in metastatic melanoma. From a comprehensive collection of melanoma cell lines, we observed that MITF methylated cultures were subdivided in two distinct subtypes. Examining mRNA levels of neural crest associated genes we found that one subtype had lost the expression of several lineage genes including SOX10. Intriguingly, SOX10 loss was associated with SOX10 gene promoter hypermethylation and distinct phenotypic and metastatic properties. Depletion of SOX10 in MITF methylated melanoma cells using CRISPR/Cas9 confirmed these findings. In conclusion, this study describes the significance of melanoma state and the underlying functional properties explaining the aggressiveness of such states.

Department/s

  • Melanoma
  • LUCC: Lund University Cancer Centre
  • Melanoma Genomics
  • Division of Clinical Genetics
  • The genetics of soft tissue tumors
  • Experimental oncology
  • Division of Translational Cancer Research
  • Lund Melanoma Study Group
  • Surgery (Lund)
  • Epilepsy Center
  • EpiHealth: Epidemiology for Health
  • Cellular Neurophysiology and Epilepsy group
  • Neurology, Lund

Publishing year

2022-10-10

Language

English

Publication/Series

JCI Insight

Volume

7

Issue

19

Document type

Journal article

Publisher

The American Society for Clinical Investigation

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Melanoma Genomics
  • The genetics of soft tissue tumors
  • Experimental oncology
  • Lund Melanoma Study Group
  • Cellular Neurophysiology and Epilepsy group

ISBN/ISSN/Other

  • ISSN: 2379-3708