Dong L, Yu Y, Yu J P, Hao W J, Zheng X Q, Cheng Y N, Han L, Zhao J Z, Gao M
Department of Thyroid and Neck Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
Cancer Molecular Diagnostic Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.
Zhonghua Zhong Liu Za Zhi. 2017 Jan 23;39(1):24-28. doi: 10.3760/cma.j.issn.0253-3766.2017.01.005.
To screen genes related to familial non-medullary thyroid carcinoma (FNMTC) using next-generation sequencing (NGS). 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. 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 (= 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 (= 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 (=0.019). 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.
采用二代测序（NGS）技术筛选与家族性非髓样甲状腺癌（FNMTC）相关的基因。设计了一组NGS检测，分别对FNMTC患者和散发性非髓样甲状腺癌（SNMTC）病例外周血白细胞提取的DNA样本进行测序，并筛选基因突变。此外，比较了有或无基因突变患者的临床病理特征，包括肿瘤大小、手术范围、淋巴结转移和甲状腺外侵犯情况。在63份非髓样甲状腺癌样本中，检测到13个基因上的45个突变。47例FNMTC患者中检测到37个种系突变，16例SNMTC患者中检测到8个种系突变。在8个FNMTC家族谱系中，来自同一谱系的FNMTC患者携带相同的突变。47例FNMTC患者中突变携带者有29例，16例SNMTC患者中突变携带者有6例，差异无统计学意义（P = 0.092）。在FNMTC患者中，29例突变阳性患者中有22例发生中央区淋巴结转移，明显多于16例突变阴性患者中的7例（P = 0.031）。就亲代而言，7例亲代患者中有3例发生中央区淋巴结受累，而9例子代患者均有中央区淋巴结转移（P=0.019）。该NGS检测可用于筛选FNMTC患者的突变易感基因，研究结果可能有助于早期发现FNMTC患者并预测其家族成员的疾病风险。
