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. 2021 May 20;12(5):781.
doi: 10.3390/genes12050781.

Clinical and Molecular Features of Skin Malignancies in Muir-Torre Syndrome

Dario Simic  1   2 , Reinhard Dummer  2 , Sandra N Freiberger  2   3 , Egle Ramelyte  1   2 , Marjam-Jeanette Barysch  1   2
Affiliations

Clinical and Molecular Features of Skin Malignancies in Muir-Torre Syndrome

Dario Simic et al. Genes (Basel). .

Abstract

Background: We investigated the mutational landscape of skin tumors in patients with Muir-Torre Syndrome (MTS) a hereditary autosomal dominant mismatch repair disorder of increased cancer susceptibility, and examined mutations other than in the DNA mismatch repair (MMR) genes.

Methods: This retrospective single-center case series included seven patients with the diagnosis of Muir-Torre Syndrome with precise medical history and family history. Mutational analysis of tumor samples Formalin-fixed paraffin-embedded tissue blocks of skin lesions associated with Muir-Torre Syndrome were used for further analysis. All skin tumors were analyzed with the Oncomine Comprehensive Assay v3 (Life Technologies), which includes 161 of the most relevant cancer driver genes.

Results: Eleven skin neoplasms (nine sebaceous tumors, one melanoma, one cutaneous squamous cell carcinoma) were diagnosed in seven patients. In two patients, visceral malignancies preceded the diagnosis of the skin tumors and one patient was diagnosed with a visceral malignancy after a sebaceous tumor. History of familial cancer of Lynch Syndrome (LS) was reported in three patients. The most frequently detected mutation was in the MSH2 gene, followed by mutations in the NOTCH1/2 and TP53 gene. Conclusion, this study provides a molecular analysis of Muir-Torre Syndrome associated and non-associated skin tumors in patients with Muir-Torre Syndrome. Patients with sebaceous lesions should undergo microsatellite instability analysis and accurate evaluation of personal and family history to detect a possible Muir-Torre syndrome. As secondary malignancies may appear years after the first occurrence of sebaceous tumors, lifelong screening is mandatory.

Keywords: Muir-Torre Syndrome; family history; molecular analysis; next-generation sequencing.

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Conflict of interest statement

Reinhard Dummer has intermittent, project focused consulting and/or advisory relationships with Novartis, Merck Sharp and Dhome (MSD), Bristol-Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator outside the submitted work. Egle Ramelyte has intermittent, project focused consulting relationships with Amgen, BMS and Sanofi outside the submitted work. Other authors have no interests to declare.

Figures

Figure 1
Figure 1
Abdominal sebaceoma patient 2. Faintly pinkish to skin-colored papule with dermoscopically yellowish ovoid areas and arborizing vessels.
Figure 2
Figure 2
Histology of a sebaceoma abdomen patient 2 (hematoxylin and eosin stain). Circumscribed basaloid tumor with sebaceous differentiation and mitosis.
Figure 3
Figure 3
(a) Pedigree of patient 1 shows the autosomal dominant transmission of skin and visceral tumors; (b) patient 7 with MTS associated tumors in family members (c); patient 7 has a brother with a lung tumor; (d) Legend.
See this image and copyright information in PMC

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