AUTHOR=Hu Yuhan , Zhu Qiang , Dai Xuan , Zhang Mengni , Chen Nanxiao , Wang Haoyu , Wang Yuting , Cao Yueyan , Wang Yufang , Zhang Ji 

TITLE=Exploration of identifying individual tumor tissue based on probabilistic model

JOURNAL=Frontiers in Oncology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1297135

DOI=10.3389/fonc.2024.1297135

ISSN=2234-943X

ABSTRACT=<p>Variations in the tumor genome can result in allelic changes compared to the reference profile of its homogenous body source on genetic markers. This brings a challenge to source identification of tumor samples, such as clinically collected pathological paraffin-embedded tissue and sections. In this study, a probabilistic model was developed for calculating likelihood ratio (<italic>LR</italic>) to tackle this issue, which utilizes short tandem repeat (STR) genotyping data. The core of the model is to consider tumor tissue as a mixture of normal and tumor cells and introduce the incidence of STR variants (<italic>φ</italic>) and the percentage of normal cells (<italic>M<sub>xn</sub></italic>) as <italic>a priori</italic> parameters when performing calculations. The relationship between <italic>LR</italic> values and <italic>φ</italic> or <italic>M<sub>xn</sub></italic> was also investigated. Analysis of tumor samples and reference blood samples from 17 colorectal cancer patients showed that all samples had <italic>Log</italic><sub>10</sub>(<italic>LR</italic>) values greater than 10<sup>14</sup>. In the non-contributor test, 99.9% of the quartiles had <italic>Log</italic><sub>10</sub>(<italic>LR</italic>) values less than 0. When the defense’s hypothesis took into account the possibility that the tumor samples came from the patient’s relatives, <italic>LR</italic> greater than 0 was still obtained. Furthermore, this study revealed that <italic>LR</italic> values increased with decreasing <italic>φ</italic> and increasing <italic>M<sub>xn</sub></italic>. Finally, <italic>LR</italic> interval value was provided for each tumor sample by considering the confidence interval of <italic>M<sub>xn</sub></italic>. The probabilistic model proposed in this paper could deal with the possibility of tumor allele variability and offers an evaluation of the strength of evidence for determining tumor origin in clinical practice and forensic identification.</p>