Tumor genetic heterogeneity analysis of chronic sun-damaged melanoma

Research output: Contribution to journalArticle

Abstract

Chronic sun-damaged (CSD) melanoma represents 10%-20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra-deep targeted sequencing of 40 cancer-associated genes was performed in 72 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole exome and RNA sequencing on multiple regions of primary tumor and multiple in-transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma-related genes or in mutational load between in situ and invasive CSDhigh lesions, while this difference was observed in CSDlow lesions. In addition, increased frequency of BRAF V600K, NF1, and TP53 mutations (p < .01, Fisher's exact test) was found in CSDhigh melanomas. Sequencing of multiple specimens from one CSDhigh patient revealed strikingly limited ITH with >95% shared mutations. Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes.

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Cancer and Oncology
Original languageEnglish
Pages (from-to)480-489
Number of pages10
JournalPigment Cell & Melanoma Research
Volume33
Issue number3
Early online date2019 Dec 7
Publication statusPublished - 2020 May
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

© 2019 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.

Related research output

Adriana Sanna, 2020, Lund: Lund University, Faculty of Medicine. 90 p.

Research output: ThesisDoctoral Thesis (compilation)

View all (1)

Related projects

View all (1)