High Prevalence of Alterations in DNA Mismatch Repair Genes of Lynch Syndrome in Pediatric Patients with Adrenocortical Tumors Carrying a Germline Mutation on TP53

Cancers

SheilaAparecida Coelho Siqueira¹  MariaClaudia Nogueira Zerbini¹  AntonioMarcondes Lerario²  MarianaFerreira de Assis Funari³  Luciana Montenegro³  MirianYumie Nishi³  BrenoMarchiori Magalhães⁴  MariaCandida Barisson Villares Fragoso⁴  VaniaBalderrama Brondani⁴  AmandaMeneses Ferreira Lacombe⁴  AnaClaudia Latronico⁴  MadsonQueiroz Almeida⁴  BereniceBilharinho Mendonca⁴  Amandade Moraes Narcizo⁵  LaisCavalca Cardoso⁵  IbereCauduro Soares⁶  FranciscoTibor Denes⁷ 

[1] Departamento de Anatomia Patológica, Faculdade de Medicina da Universidade de São Paulo, São Paulo 0540396, Brasil;Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA;Laboratório de Hormônios e Genética Molecular LIM/42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 0540396, Brasil;Laboratório de Hormônios e Genética Molecular LIM/42, Unidade de Suprarrenal, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 0540396, Brasil;Laboratório de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina da Universidade de São Paulo, São Paulo 0540396, Brasil;Serviço de Anatomia Patológica, Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo 0540396, Brasil;Serviço de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 0540396, Brasil;

关键词: adrenal tumor;    dna mismatch repair;    tp53;   

DOI  :  10.3390/cancers12030621

来源: DOAJ

【 摘 要 】

Adrenocortical cancer is a rare malignant neoplasm associated with a dismal prognosis. Identification of the molecular pathways involved in adrenal tumorigenesis is essential for a better understanding of the disease mechanism and improvement of its treatment. The aim of this study is to define the prevalence of alterations in DNA mismatch repair (MMR) genes in Lynch syndrome among pediatric patients with adrenocortical neoplasia from southern Brazil, where the prevalence of a specific TP53 germline mutation (p.Arg337His) is quite high. Thirty-six pediatric patients were retrospectively evaluated. Immunohistochemistry (IHC) for the MMR enzymes MLH1, MSH2, MSH6, and PMS2, as well as next-generation sequencing (NGS) were performed. For IHC, 36 pediatric tumors were tested. In all of them, the expression of all evaluated MMR proteins was well-preserved. For NGS, 35 patients with pediatric tumor were tested. Three patients (8.57%) with the TP53 p.Arg337His germline mutation presented pathogenic and likely pathogenic variants in the MMR genes (two in MLH1 and one in MSH6). The prevalence of altered MMR genes among pediatric patients was elevated (8.57%) and higher than in colorectal and endometrial cancer cohorts. Pediatric patients with adrenocortical tumors should, thus, be strongly considered as at genetic risk for Lynch syndrome.

【 授权许可】

Unknown