Objective: To screen genes related to familial non-medullary thyroid carcinoma (FNMTC) using next-generation sequencing (NGS). Methods: A panel of NGS was designed and sequencing was performed for DNA samples extracted from peripheral blood leukocytes of FNMTC patients and sporadic non-medullary thyroid carcinoma (SNMTC) cases, respectively, and gene mutations were screened. In addition, the clinicopathological characteristics, including tumor size, extension of surgery, lymph node metastasis and extra-thyroidal extension, were compared between patients with or without mutations. Results: In 63 NMTC samples, 45 mutations were detected on 13 genes. 37 germline mutations were detected in 47 FNMTC patients, while 8 germline mutations were detected in 16 SNMTC patients. In 8 FNMTC family lineages, the same mutations were carried by FNMTC patients from the same pedigree. The number of carriers of mutations was 29 in the 47 FNMTC patients and 6 in the 16 SNMTC patients, with a non-significant difference (P= 0.092). Among the FNMTC patients, there were 22 patients with central lymph node metastasis in the 29 mutation-positive patients, significantly more than 7 in the 16 mutation-negative cases (P= 0.031). As for the parentage, there were 3 patients with central lymph node involvement among the 7 patients of parent generation, while all the 9 patients of offspring generation had central lymph node metastasis (P=0.019). Conclusions: This panel of NGS can be used to screen mutant susceptibility gene of FNMTC patients, and the findings may be helpful for early detection of FNMTC patients and predicting the disease risk to familial members of FNMTC patients.
目的： 利用二代测序技术筛查非髓样甲状腺癌(NMTC)的遗传易感基因。 方法： 收集家族性非髓样甲状腺癌(FNMTC)和散发性非髓样甲状腺癌(SNMTC)患者的外周血，提取DNA。针对遗传性甲状腺癌相关基因的全外显子区域进行探针杂交捕获测序，筛查基因突变位点。 结果： 在63例NMTC样本中，共发现分别位于13个基因的45个高质量的胚系突变。其中在47例FNMTC患者中发现37个突变，在16例SNMTC患者中发现8个突变。在8个FNMTC家系中，发现同一家系的患者携带相同的突变位点。在47例FNMTC患者中，基因突变携带者29例；16例SNMTC患者中，基因突变携带者6例，差异无统计学意义(P＝0.092)。FNMTC患者中，基因突变组(29例)和基因未突变组(16例)中中央区淋巴结转移患者分别为22例和7例，差异有统计学意义(P＝0.031)。在具有亲子关系的患者中，7例亲代患者中，有中央区淋巴结转移3例；9例子代患者均有中央区淋巴结转移，差异有统计学意义(P＝0.019)。 结论： 二代测序技术可用于筛查FNMTC患者特异性的遗传易感基因变异，有助于早期发现FNMTC患者和预测甲状腺癌患者家族成员的发病风险。.
Keywords: Early diagnosis; Genetic predisposition to disease; Genetic testing; Multilocus sequence typing; Thyroid neoplasms.