Martins-Costa Maria Cecília, Lindsey Susan C, Cunha Lucas L, Carreiro-Filho Fernando Porto, Cortez André P, Holanda Marcelo E, Farias J Wilson M de, Lima Sérgio B, Ferreira Luís A Albano, Maia Filho Pedro Collares, Camacho Cléber P, Furuzawa Gilberto K, Kunii Ilda S, Dias-da-Silva Magnus R, Martins João R M, Maciel Rui M B
Centro de Doenças da Tiroide e Laboratório de Endocrinologia Molecular e Translacional, Divisão de Endocrinologia, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brasil.
Centro de Endocrinologia e Metabologia, Hospital Geral de Fortaleza (HGF), Fortaleza, CE, Brasil.
Arch Endocrinol Metab. 2018;62(6):623-635. doi: 10.20945/2359-3997000000088.
Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening.
We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Direct genetic sequencing was used to analyze exons 8, 10, 11, and 13-16 in MTC index cases and specific exons in at risk relatives. Afterward, clinical follow-up was offered to all the patients with MTC and their affected relatives.
RET screening was performed in 60 MTC index patients and 187 at-risk family members. At the initial clinical assessment of the index patients, 54 (90%) were diagnosed with apparently sporadic disease and 6 (10%) diagnosed with hereditary disease. After RET screening, we found that 31 (52%) index patients had sporadic disease, and 29 (48%) had hereditary disease. Regarding at-risk relatives, 73/187 were mutation carriers. Mutations in RET codon 804 and the rare p.M918V mutation were the most prevalent.
Performing RET screening in Ceará allowed us to identify a different mutation profile in this region compared with other areas. RET screening also enabled the diagnosis of a significant number of hereditary MTC patients who were initially classified as sporadic disease patients and benefited their relatives, who were unaware of the risks and the consequences of bearing a RET mutation.
甲状腺髓样癌（MTC）的初始诊断常与晚期疾病及不良预后相关。因此，对于有患病风险的亲属进行更早诊断和检测的需求促使RET基因筛查的使用增加。
我们对247名转诊至塞阿拉州巴西多内分泌腺瘤病研究联盟（BRASMEN）中心的受试者进行了RET筛查。直接基因测序用于分析MTC索引病例中的第8、10、11和13 - 16外显子以及有患病风险亲属中的特定外显子。之后，对所有MTC患者及其受影响的亲属进行了临床随访。
对60名MTC索引患者和187名有患病风险的家庭成员进行了RET筛查。在索引患者的初始临床评估中，54名（90%）被诊断为明显散发型疾病，6名（10%）被诊断为遗传性疾病。经过RET筛查后，我们发现31名（52%）索引患者患有散发型疾病，29名（48%）患有遗传性疾病。对于有患病风险的亲属，73/187为突变携带者。RET密码子804的突变和罕见的p.M918V突变最为常见。
在塞阿拉州进行RET筛查使我们发现该地区与其他地区不同的突变谱。RET筛查还能够诊断出大量最初被归类为散发型疾病患者的遗传性MTC患者，并使他们未意识到携带RET突变风险和后果的亲属受益。
