Chen Anqi, Xiong Lei, Qu Yiling, Xi Shihan, Tao Ruiyang, Li Chengtao, Zhang Suhua
Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Science, Ministry of Justice, Shanghai, China.
Department of Forensic Medicine, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Front Oncol. 2022 Feb 11;12:800028. doi: 10.3389/fonc.2022.800028. eCollection 2022.
Personal identification using the tumor DNA not only plays an important role in postoperative tissue management but also might be the only accessible source of biological material in forensic identification. Short tandem repeat (STR) is the worldwide accepted forensic marker; however, widespread loss of heterozygosity (L) in tumor tissues challenges the personal identification using the conventional capillary electrophoresis (CE)-based STR typing system (CE-STR). Because the tumors are mixtures of tumor cells and basal cells, we inferred that every germline-originated allele should be detected if the detection method was sensitive enough. Next-generation sequencing (NGS) is known as a highly sensitive application, which might be a promising tool for tumor source identification. In the study, we genotyped and compared the STR results between the platforms, and we found that the concordance was only 91.43%. Higher sensitivity did help identify more germline-originated alleles as expected, and 93.89% of them could be captured by using an NGS-based STR system (NGS-STR). The identity-by-state (IBS) scoring system was applied to generate a new tumor source identification method based on NGS-STR, and the number of loci with 2 identical alleles (A) proved to be an ideal criterion for the larger area under the receiver operating characteristic (ROC) curve (AUC). Both the sensitivity and specificity were above 98% in the cutoff of A to distinguish the paired carcinoma (PC) sample group from the unrelated individual (UI) group, the simulated full sibling (FS) group, and the simulated parent-offspring (PO) group.
利用肿瘤DNA进行个人识别不仅在术后组织管理中发挥重要作用，而且可能是法医鉴定中唯一可获取的生物材料来源。短串联重复序列（STR）是全球公认的法医标记；然而，肿瘤组织中广泛存在的杂合性缺失（L）对使用传统基于毛细管电泳（CE）的STR分型系统（CE-STR）进行个人识别提出了挑战。由于肿瘤是肿瘤细胞和基底细胞的混合物，我们推断，如果检测方法足够灵敏，每个种系起源的等位基因都应能被检测到。下一代测序（NGS）是一种高灵敏度的应用，可能是肿瘤来源鉴定的一种有前途的工具。在本研究中，我们对不同平台的STR结果进行基因分型和比较，发现一致性仅为91.43%。更高的灵敏度确实有助于如预期那样识别更多种系起源的等位基因，其中93.89%的等位基因可通过基于NGS的STR系统（NGS-STR）捕获。应用状态相同（IBS）评分系统基于NGS-STR生成一种新的肿瘤来源鉴定方法，具有两个相同等位基因（A）的位点数量被证明是在受试者工作特征（ROC）曲线下面积（AUC）更大时的理想标准。在区分配对癌（PC）样本组与无关个体（UI）组、模拟全同胞（FS）组和模拟亲子（PO）组时，A的临界值下灵敏度和特异性均高于98%。
