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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 2 ) 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 2  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.

Opportunity of Next-Generation Sequencing-Based Short Tandem Repeat System for Tumor Source Identification