Brondani Vania Balderrama, Montenegro Luciana, Lacombe Amanda Meneses Ferreira, Magalhães Breno Marchiori, Nishi Mirian Yumie, Funari Mariana Ferreira de Assis, Narcizo Amanda de Moraes, Cardoso Lais Cavalca, Siqueira Sheila Aparecida Coelho, Zerbini Maria Claudia Nogueira, Denes Francisco Tibor, Latronico Ana Claudia, Mendonca Berenice Bilharinho, Almeida Madson Queiroz, Lerario Antonio Marcondes, Soares Ibere Cauduro, Fragoso Maria Candida Barisson Villares
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 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.
Cancers (Basel). 2020 Mar 7;12(3):621. doi: 10.3390/cancers12030621.
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 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 p.Arg337His germline mutation presented pathogenic and likely pathogenic variants in the genes (two in and one in ). The prevalence of altered 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.
肾上腺皮质癌是一种罕见的恶性肿瘤，预后较差。确定参与肾上腺肿瘤发生的分子途径对于更好地理解疾病机制和改善其治疗至关重要。本研究的目的是确定巴西南部患有肾上腺皮质肿瘤的儿科患者中林奇综合征（Lynch syndrome）DNA错配修复（MMR）基因改变的患病率，在该地区一种特定的种系突变（p.Arg337His）的患病率相当高。对36例儿科患者进行了回顾性评估。进行了MMR酶MLH1、MSH2、MSH6和PMS2的免疫组织化学（IHC）以及二代测序（NGS）。对于IHC，检测了36例儿科肿瘤。在所有肿瘤中，所有评估的MMR蛋白的表达均保存良好。对于NGS，检测了35例患有儿科肿瘤的患者。3例（8.57%）携带p.Arg337His种系突变的患者在这些基因中出现了致病和可能致病的变异（2例在[具体基因1]，1例在[具体基因2]）。儿科患者中基因改变的患病率升高（8.57%），高于结直肠癌和子宫内膜癌队列。因此，患有肾上腺皮质肿瘤的儿科患者应被强烈视为具有林奇综合征的遗传风险。
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