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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. 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. [ABSTRACT FROM AUTHOR]

Background Precision oncology, guided by high-resolution molecular diagnostics, refers to the ability to identify patients that are likely to respond to specific anticancer therapies. Although recent studies demonstrated the utility of comprehensive molecular profiling based on whole-exome/genome sequencing and transcriptome sequencing to guide therapeutic decisions in individual patients, many questions remain unanswered. Methods We report the clinical results of MASTER, a multicenter, cross-entity registry trial for prospective, biology-driven stratification of younger adults with advanced-stage cancer and patients with rare tumors conducted by NCT Heidelberg/Dresden and the German Cancer Consortium. From 2013 to 2018, we discussed the molecular profiles from 1,311 poor-prognosis patients in a cross-institutional molecular tumor board. Results Evaluation of the data based on a standardized bioinformatics workflow and manual curation by a team of translational oncologists allowed categorization into 7 intervention baskets and formulation of evidence-based recommendations for clinical management in more than 80% of patients, which could be acted upon in approximately one third of cases. Overall response and disease control rates on molecularly guided treatment were improved compared to prior systemic therapies, which translated into a progression-free survival ratio of greater than 1.3 in more than 30% of cases. Comprehensive genomic profiling also provided relevant diagnostic information that led to categorization of some tumors based on genotype and subsequent histopathologic reevaluation. Conclusions Our experience demonstrates that comprehensive molecular profiling in a multi-institutional clinical setting is feasible, complements and advances routine molecular diagnostics, and creates clinically meaningful therapeutic opportunities. Current and future initiatives of the MASTER network are focused on the standardization of variant classification and evidence levels in molecular tumor boards; the implementation of molecularly stratified basket trials; and the integration of additional layers of patient characterization. Legal entity responsible for the study The authors. Funding German Cancer Consortium, Heidelberg Institute for Personalized Oncology. Disclosure W. Weichert: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Research grant / Funding (self): Bruker. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]