Cutaneous epithelioid haemangiomas show somatic mutations in the mitogen‐activated protein kinase pathway. (21st December 2021)

• Record Type: Journal Article
• Authors: Maurus, K.; Kosnopfel, C.; Kneitz, H.; Appenzeller, S.; Schrama, D.; Glutsch, V.; Roth, S.; Gerhard‐Hartmann, E.; Rosenfeldt, M.; Möhrmann, L.; Fröhlich, M.; Hübschmann, D.; Stenzinger, A.; Glimm, H.; Fröhling, S.; Goebeler, M.; Rosenwald, A.; Kutzner, H.; Schilling, B.
• Is Part Of: British journal of dermatology. Volume 186:Number 3(2022)
• Page Start: 553
• Page End: 563
• Publication Date: 2021-12-21
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.20869
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Background: Epithelioid haemangioma (EH) arising from the skin is a benign vascular tumour with marked inflammatory cell infiltration, which exhibits a high tendency to persist and frequently recurs after resection. So far, the underlying pathogenesis is largely elusive. Objectives: To identify genetic alterations by next‐generation sequencing and/or droplet digital polymerase chain reaction (ddPCR) in cutaneous EH. Methods: DNA and RNA from an EH lesion of an index patient were subjected to whole‐genome and RNA sequencing. Multiplex PCR‐based panel sequencing of genomic DNA isolated from archival formalin‐fixed paraffin‐embedded tissue of 18 patients with cutaneous EH was performed. ddPCR was used to confirm mutations. Results: We identified somatic mutations in genes of the mitogen‐activated protein kinase (MAPK) pathway ( MAP2K1 and KRAS ) in cutaneous EH biopsies. By ddPCR we could confirm the recurrent presence of activating, low‐frequency mutations affecting MAP2K1 . In total, nine out of 18 patients analysed showed activating MAPK pathway mutations, which were mutually exclusive. Comparative analysis of tissue areas enriched for lymphatic infiltrate or aberrant endothelial cells, respectively, revealed an association of these mutations with the presence of endothelial cells. Conclusions: Taken together, our data suggest that EH shows somatic mutations in genes of the MAPK pathway which might contribute to the formation of this benign tumour. Abstract : What is already known about this topic? Epithelioid haemangioma (EH) arising from the skin is a benign vascular tumour of unknown aetiology. Cutaneous EH often shows a marked inflammatory infiltrate indicating a reactive origin. What does this study add? Half of the samples from cutaneous EH in this study showed activating mutations in the mitogen‐activated protein kinase pathway ( MAP2K1 and KRAS ). Mutations were mutually exclusive. What is the translational message? Somatic mutations seem to contribute to the formation of a significant proportion of cutaneous EH. The molecular alterations found might be sensitive for targeted therapies. Linked Comment: W. Tan and J.S. Nelson. Br J Dermatol 2022; 186 :393–394 .