Tumor genetic heterogeneity analysis of chronic sun‐damaged melanoma. (23rd December 2019)

• Record Type: Journal Article
• Authors: Sanna, Adriana; Harbst, Katja; Johansson, Iva; Christensen, Gustav; Lauss, Martin; Mitra, Shamik; Rosengren, Frida; Häkkinen, Jari; Vallon‐Christersson, Johan; Olsson, Håkan; Ingvar, Åsa; Isaksson, Karolin; Ingvar, Christian; Nielsen, Kari; Jönsson, Göran
• Is Part Of: Pigment cell & melanoma research. Volume 33:Number 3(2020)
• Page Start: 480
• Page End: 489
• Publication Date: 2019-12-23
• Subjects: chronic sun damage -- heterogeneity -- in situ -- invasive -- melanoma; Melanoma -- Periodicals; Chromatophores -- Periodicals; Animal pigments -- Periodicals; 616.99477
• DOI: 10.1111/pcmr.12851
• Languages: English
• ISSNs: 1755-1471

Abstract

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