与其同源体源在遗传标记上的参考谱相比,肿瘤基因组中的变异可导致等位基因变化。这给肿瘤样本的来源鉴定带来了挑战,如临床收集的病理石蜡包埋组织和切片。在这项研究中,开发了一个概率模型来计算似然比(LR)来解决这个问题,它利用短串联重复序列(STR)基因分型数据。该模型的核心是将肿瘤组织视为正常细胞和肿瘤细胞的混合物,并在执行计算时引入STR变体的发生率(Φ)和正常细胞的百分比(Mxn)作为先验参数。还研究了LR值与φ或Mxn之间的关系。来自17名结肠直肠癌患者的肿瘤样品和参考血液样品的分析显示,所有样品的Log10(LR)值大于1014。在非贡献者测试中,99.9%的四分位数具有小于0的Log10(LR)值。当辩方的假设考虑到肿瘤样本来自患者亲属的可能性时,仍然获得了大于0的LR。此外,这项研究表明,LR值随着φ的减小和Mxn的增加而增加。最后,通过考虑Mxn的置信区间,为每个肿瘤样品提供LR区间值。本文提出的概率模型可以处理肿瘤等位基因变异性的可能性,并为临床实践和法医学鉴定中确定肿瘤起源的证据强度提供了评估。
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 (LR) 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 (φ) and the percentage of normal cells (Mxn) as a priori parameters when performing calculations. The relationship between LR values and φ or Mxn was also investigated. Analysis of tumor samples and reference blood samples from 17 colorectal cancer patients showed that all samples had Log 10(LR) values greater than 1014. In the non-contributor test, 99.9% of the quartiles had Log 10(LR) values less than 0. When the defense\'s hypothesis took into account the possibility that the tumor samples came from the patient\'s relatives, LR greater than 0 was still obtained. Furthermore, this study revealed that LR values increased with decreasing φ and increasing Mxn. Finally, LR interval value was provided for each tumor sample by considering the confidence interval of Mxn. 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.