Genetic heterogeneity in a patient with Muir-Torre syndrome
| Autor: | Chinmoy Bhate, Ruonan Zhang, Donghong Cai |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Keratoacanthoma
Pathology medicine.medical_specialty Skin Neoplasm business.industry Genetic heterogeneity Microsatellite instability Case Report Muir-Torre syndrome MMR mismatch repair Dermatology lcsh:RL1-803 medicine.disease SCC squamous cell carcinoma digestive system diseases Sebaceous adenoma genetic heterogeneity Germline mutation Muir–Torre syndrome lcsh:Dermatology PMS2 Medicine business sebaceous adenoma MMR genes |
| Zdroj: | JAAD Case Reports JAAD Case Reports, Vol 6, Iss 9, Pp 886-891 (2020) |
| ISSN: | 2352-5126 |
| Popis: | Muir-Torre syndrome is an autosomal-dominant disorder caused by germline mutations in 1 of the 4 key DNA mismatch repair (MMR) genes, MSH2, MSH6, PMS2, and MLH1. Patients with Muir-Torre syndrome present with skin lesions, which play an important role in early detection of the disease and are considered cutaneous markers. The diagnostic criteria for Muir-Torre syndrome are at least 1 skin neoplasm with sebaceous differentiation, at least 1 visceral malignancy, and germline mutation of the MMR genes.1,2 Sebaceous adenoma is rare and is considered the most significant cutaneous marker for Muir-Torre syndrome.3 Abbas and Mahalingam4 suggested that when a young patient presents with a sebaceous neoplasm outside the head and neck area, immunohistochemical analysis of the MMR genes should be conducted for Muir-Torre syndrome screening. If loss of any MMR proteins is identified, microsatellite instability study or germline analysis is warranted for further diagnosis. In addition, presence of multiple keratoacanthomas should also prompt immunostaining studies for screening.3 In Muir-Torre syndrome, the keratoacanthoma usually presents with sebaceous differentiation.3 For a specific patient, loss of MMR proteins in the skin lesions and in the visceral tumors should be in concordance because of the presence of germline mutation. However, here we examined a visceral tumor and all 16 skin lesions from a patient with Muir-Torre syndrome and found genetic heterogeneity among several samples. All 13 sebaceous adenomas and the visceral tumor showed the same expression pattern of the MMR genes in line with the germline mutation, whereas other skin lesions such as keratoacanthoma and squamous cell carcinoma (SCC) showed aberrant expression patterns. To our knowledge, this is the first study reporting the phenomenon of genetic heterogeneity in a Muir-Torre syndrome patient. |
| Databáze: | OpenAIRE |
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