Clinical and Molecular Assessment of Patients with Lynch Syndrome and Sarcomas Underpinning the Association with MSH2 Germline Pathogenic Variants
| Autor: | Mariana Petaccia de Macedo, Maria Nirvana Formiga, Maria Leticia Gobo Silva, Vanessa Nascimento Kozak, Nathália de Angelis de Carvalho, Samuel Aguiar Junior, José Cláudio Casali-da-Rocha, Sahlua Volc, Giovana Tardin Torrezan, Edenir Inêz Palmero, Felipe D´Almeida Costa, Bruna Elisa Catin Kupper, Bianca Naomi Niitsuma, Dirce Maria Carraro |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology congenital hereditary and neonatal diseases and abnormalities Cancer Research medicine.medical_specialty sarcoma Liposarcoma MLH1 lcsh:RC254-282 Germline 03 medical and health sciences 0302 clinical medicine Internal medicine medicine MSH2 germline variant neoplasms Genetic testing medicine.diagnostic_test business.industry mismatch repair deficiency nutritional and metabolic diseases Microsatellite instability lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Lynch syndrome digestive system diseases 030104 developmental biology hereditary cancer MSH2 030220 oncology & carcinogenesis Sarcoma business |
| Zdroj: | Cancers Volume 12 Issue 7 Cancers, Vol 12, Iss 1848, p 1848 (2020) |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers12071848 |
| Popis: | Lynch syndrome (LS) is a hereditary cancer-predisposing syndrome associated most frequently with epithelial tumors, particularly colorectal (CRC) and endometrial carcinomas (EC). The aim of this study was to investigate the relationship between sarcomas and LS by performing clinical and molecular characterization of patients presenting co-occurrence of sarcomas and tumors from the LS spectrum. We identified 27 patients diagnosed with CRC, EC, and other LS-associated tumors who had sarcomas in the same individuals or families. Germline genetic testing, mismatch repair (MMR) protein immunohistochemistry, microsatellite instability (MSI), and other molecular analyses were performed. Five LS patients presenting personal or family history of sarcomas were identified (3 MSH2 carriers and 2 MLH1), with 2 having Muir&ndash Torre phenotypes. For two MSH2 carriers we confirmed the etiology of the sarcomas (one liposarcoma and two osteosarcomas) as LS-related, since the tumors were MSH2/MSH6-deficient, MSI-high, or presented a truncated MSH2 transcript. Additionally, we reviewed 43 previous reports of sarcomas in patients with LS, which revealed a high frequency (58%) of MSH2 alterations. In summary, sarcomas represent a rare clinical manifestation in patients with LS, especially in MSH2 carriers, and the analysis of tumor biological characteristics can be useful for definition of tumor etiology and novel therapeutic options. |
| Databáze: | OpenAIRE |
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