Comparison of the Allelic Alterations between InDel and STR Markers in Tumoral Tissues Used for Forensic Purposes

Abstract

Background and objectives: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.

Exploration of identifying individual tumor tissue based on probabilistic model

“…classified the STR variants observed in tumor tissue into three categories as follows: 1. the additional alleles (Aadd), 2. the new alleles instead of somatic-derived alleles (Anew), and 3. partial or complete loss of heterozygosity (pLOH/LOH), and provided criteria to distinguish LOH from pLOH ( 13 ). The possibility of using nuclear genomic SNPs ( 14 , 15 ) and indels ( 16 ), along with mitochondrial SNPs ( 5 , 17 ) has also been investigated for tumor source identification. However, the aforementioned retrospective study analyzed the existing experimental data empirically.…”

“…Nevertheless, this approach was constrained by the sample size and lacked a statistical metric to quantify the strength of the evidence, i.e., the genotyping profile makes the tumor sample originating from the person of interest more or less probable. Furthermore, the genetic marker indel, which is more significant in mutations, cannot be used to identify the body origin of tumor tissue ( 16 ). This is also the case for mitochondrial SNPs due to their heterogeneity.…”

Uso de marcadores informativos de ancestralidade para desenvolvimento de painéis de inferência de ancestralidade e identificação humana em populações miscigenadas

“…São polimorfismos de comprimento, caracterizados pela inserção ou deleção de um ou mais nucleotídeos em uma determinada região do genoma. Como os SNPs, apresentam baixa informatividade, sendo necessário um grande número de InDels para um resultado semelhante a um ensaio utilizando STRs (Tozzo et al, 2021). Entretanto, apresentam a maioria das vantagens anteriormente relatadas para os SNPs, além de poder ser analisado por PCR seguida de eletroforese.…”