Clinical and Molecular Assessment of Patients with Lynch Syndrome and Sarcomas Underpinning the Association withMSH2Germline Pathogenic Variants

Author(s):Show less -

de Carvalho, Nathalia de Angelis ^[1] ; Niitsuma, Bianca Naomi ^[1] ; Kozak, Vanessa Nascimento ^{[2, 3]} ; Costa, Felipe D'almeida ^[4] ; de Macedo, Mariana Petaccia ^[4] ; Catin Kupper, Bruna Elisa ^[5] ; Gobo Silva, Maria Leticia ^[6] ; Formiga, Maria Nirvana ^[7] ; Volc, Sahlua Miguel ^{[8, 9]} ; Aguiar Junior, Jr., Samuel ^[5] ; Palmero, Edenir Inez ^{[8, 10, 11]} ; Casali-da-Rocha, Jose Claudio ^{[7, 2]} ; Carraro, Dirce Maria ^{[1, 12]} ; Torrezan, Giovana Tardin ^{[1, 12]}

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^[1] AC Camargo Canc Ctr, Int Res Ctr CIPE, Genom & Mol Biol Grp, BR-01508010 Sao Paulo - Brazil

^[2] Hosp Erasto Gaertner, Oncogenet Serv, BR-81520060 Curitiba, Parana - Brazil

^[3] Univ Fed Parana, Postgrad Program Genet, BR-81530000 Curitiba, Parana - Brazil

^[4] AC Camargo Canc Ctr, Anat Pathol Dept, BR-01509900 Sao Paulo - Brazil

^[5] AC Camargo Canc Ctr, Colorectal Canc Dept, BR-01509900 Sao Paulo - Brazil

^[6] AC Camargo Canc Ctr, Radiotherapy Dept, BR-01509900 Sao Paulo - Brazil

^[7] AC Camargo Canc Ctr, Oncogenet Dept, BR-01509900 Sao Paulo - Brazil

^[8] Fac Pequeno Principe, BR-80230020 Curitiba, Parana - Brazil

^[9] Barretos Canc Hosp, Oncogenet Dept, BR-14784400 Barretos - Brazil

^[10] Barretos Canc Hosp, Mol Oncol Res Ctr, BR-14784384 Barretos - Brazil

^[11] Inst Pesquisa Pele Pequeno Principe, BR-80250060 Curitiba, Parana - Brazil

^[12] Natl Inst Sci & Technol Oncogen INCITO, BR-01508010 Sao Paulo - Brazil

• Document type: Journal article
• Source: CANCERS; v. 12, n. 7 JUL 2020.
• Web of Science Citations: 0

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 (3MSH2carriers and 2MLH1), with 2 having Muir-Torre phenotypes. For twoMSH2carriers 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%) ofMSH2alterations. In summary, sarcomas represent a rare clinical manifestation in patients with LS, especially inMSH2carriers, and the analysis of tumor biological characteristics can be useful for definition of tumor etiology and novel therapeutic options. (AU)

• FAPESP's process: 18/06269-5 - Combining genomic approaches to determine the genetics causes of rare cancers in children, adolescents and young adults
• Grantee: Giovana Tardin Torrezan
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50943-1 - INCT 2014: on Oncogenomics and Therapeutic Inovations
• Grantee: Dirce Maria Carraro
• Support Opportunities: Research Projects - Thematic Grants