Tozzo Pamela, Delicati Arianna, Frigo Anna Chiara, Caenazzo Luciana
Department of Molecular Medicine, Laboratory of Forensic Genetics, University of Padova, 35121 Padova, Italy.
Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35121 Padova, Italy.
Medicina (Kaunas). 2021 Mar 2;57(3):226. doi: 10.3390/medicina57030226.
: Over the last two decades, human DNA identification and kinship tests have been conducted mainly through the analysis of short tandem repeats (STRs). However, other types of markers, such as insertion/deletion polymorphisms (InDels), may be required when DNA is highly degraded. In forensic genetics, tumor samples may sometimes be used in some cases of human DNA identification and in paternity tests. Nevertheless, tumor genomic instability related to forensic DNA markers should be considered in forensic analyses since it can compromise genotype attribution. Therefore, it is useful to know what impact tumor transformation may have on the forensic interpretation of the results obtained from the analysis of these polymorphisms. : The aim of this study was to investigate the genomic instability of InDels and STRs through the analysis of 55 markers in healthy tissue and tumor samples (hepatic, gastric, breast, and colorectal cancer) in 66 patients. The evaluation of genomic instability was performed comparing InDel and STR genotypes of tumor samples with those of their healthy counterparts. : With regard to STRs, colorectal cancer was found to be the tumor type affected by the highest number of mutations, whereas in the case of InDels the amount of genetic mutations turned out to be independent of the tumor type. However, the phenomena of genomic instability, such as loss of heterozygosity (LOH) and microsatellite instability (MSI), seem to affect InDels more than STRs hampering genotype attribution. : We suggest that the use of STRs rather than InDels could be more suitable in forensic genotyping analyses given that InDels seem to be more affected than STRs by mutation events capable of compromising genotype attribution.
在过去二十年中,人类DNA鉴定和亲属关系测试主要通过短串联重复序列(STR)分析来进行。然而,当DNA高度降解时,可能需要其他类型的标记,如插入/缺失多态性(InDel)。在法医遗传学中,肿瘤样本有时可用于某些人类DNA鉴定和亲子鉴定案例。尽管如此,由于肿瘤基因组不稳定性可能会影响基因型归属,因此在法医分析中应考虑与法医DNA标记相关的肿瘤基因组不稳定性。因此,了解肿瘤转化对这些多态性分析结果的法医解释可能产生何种影响是很有用的。
本研究的目的是通过分析66例患者的健康组织和肿瘤样本(肝癌、胃癌、乳腺癌和结直肠癌)中的55个标记,来研究InDel和STR的基因组不稳定性。通过将肿瘤样本的InDel和STR基因型与其健康对应样本的基因型进行比较,对基因组不稳定性进行评估。
关于STR,发现结直肠癌是受突变影响数量最多的肿瘤类型,而对于InDel,基因突变的数量与肿瘤类型无关。然而,基因组不稳定性现象,如杂合性缺失(LOH)和微卫星不稳定性(MSI),似乎对InDel的影响比对STR的影响更大,从而妨碍基因型归属。
我们建议,在法医基因分型分析中使用STR可能比使用InDel更合适,因为InDel似乎比STR更容易受到能够影响基因型归属的突变事件的影响。