由于大部分甲状腺微小癌惰性生长，并不危及生命，是否需要手术及手术术式均存在一定争议，因此，术前准确评估微小癌的侵袭潜能具有非常重要的临床价值。超声引导下细针穿刺能够获取患者的肿瘤细胞，通过对其进行基因检测，有望在术前评估其侵袭潜能。申请人在前期全外显子测序的结果中发现TP53、TTN、PDF等基因内可能存在与甲状腺乳头状癌侵袭性有关的SNP和Indel突变位点，但全外显子测序噪音较多，深度不够且成本高昂，为了进一步高效且经济地验证和研究目标区域，申请人设计了目标区域捕获探针库，拟对40对不同侵袭程度的新鲜甲状腺乳头状癌样本进行目标区域深度测序，进一步分析其突变的位点和形式，将其结果运用于术前FNA基因检测，并结合超声声像图特点综合评价微小癌的侵袭潜能。本研究暂不对具体基因的致病机制进行深入研究，工作量在可控范围内，与申请资助的金额匹配，极有可能达到预期研究目标。

The prevalence of papillary thyroid micro-carcinoma (PTMC) increased rapidly in recent years but the design of treatment is controversial because a majority of them are indolent. Therefore, to recognize which PTMC is of strong progressive potential which should be operated is very crucial. Fine needle aspiration (FNA) pre-surgery could obtain tumor cells which could be used in genetic analysis. To date, there is no specific way to evaluate the aggressive potential of a PTMC pre-surgery. So, the purpose of this proposal is to screen genetic mutations of the aggressive type of PTMC. The candidate did a whole exome sequencing on 3-3 pairs of PTCs and found some SNPs and Indels in TP53、TTN、PDF. To further investigate those mutations, a target region sequencing will be done in 40 pairs tumor samples. And ultimately to find out which genetic event could contribute to strong aggressive potential of PTC. The mutations details would be design to test the FNA and tissue sample to validate if the genetic testing based on FNA is reliable. The gene test results would be evaluated with sonographic features to predict the potential of small thyroid carcinoma before surgery. This project won’t aim to study the function and mechanism of specific genes but just screen them out. So, the fund would cover the fee of the whole study and this study is very likely to achieve the goal.