Clinical and Molecular Assessment of Patients with Lynch Syndrome and Sarcomas Underpinning the Association with MSH2 Germline Pathogenic Variants - PubMed

Clinical and Molecular Assessment of Patients with Lynch Syndrome and Sarcomas Underpinning the Association with MSH2 Germline Pathogenic Variants - PubMed

Clinical and Molecular Assessment of Patients with Lynch Syndrome and Sarcomas Underpinning the Association with MSH2 Germline Pathogenic Variants

Nathália de Angelis de Carvalho 1, Bianca Naomi Niitsuma 1, Vanessa Nascimento Kozak 2 3, Felipe D'almeida Costa 4, Mariana Petaccia de Macedo 4, Bruna Elisa Catin Kupper 5, Maria Letícia Gobo Silva 6, Maria Nirvana Formiga 7, Sahlua Miguel Volc 8 9, Samuel Aguiar Junior 5, Edenir Inez Palmero 8 10 11, José Cláudio Casali-da-Rocha 2 7, Dirce Maria Carraro 1 12, Giovana Tardin Torrezan 1 12

Affiliations 

• PMID: 32659967
 
• DOI: 10.3390/cancers12071848

Free article

Abstract

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-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.

Keywords: Lynch syndrome; MSH2 germline variant; hereditary cancer; mismatch repair deficiency; sarcoma.

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