Cancerous Tissues in Forensic Genetic Analysis

Abstract

Microsatellites or short tandem repeats (STRs) markers are important tools for mapping disease-causing genes by linkage, for performing investigations in forensic medicine, for population genetic studies and for studying genetic modifications in tumors. In forensic applications neoplastic tissues can be used as a source of genetic information for personal identification or paternity testing when no other specimen is available. Cancer tissues can show microsatellite instability (MSI) and loss of heterozygosity (LOH) also for the STRs used in the forensic field. In this study, we screened 56 sporadic gastrointestinal carcinomas in order to provide further data for the evaluation of the incidence of allelic alterations for 15 STR loci and the suitability of using cancerous tissues in forensic applications. Sixty-six percent of the cancerous tissues were found to possess allelic alterations of the microsatellites analyzed with a high incidence of MSI-L (microsatellite instability low) when compared to the corresponding normal tissue. The most frequently altered loci were D18S51, VWA, and FGA. From a forensic perspective, great care must be taken in evaluating the DNA typing results obtained from cancerous tissue samples.

Loss of heterozygosity (LOH)--implications for human genetic identification.

“…This prevalence is in line with the comprehensive results from 118 solid tumors, 46 lymph node metastases, and 16 distant metastases analysed with the AmpFlSTR Profiler by Poetsch et al [30]. The presented data as well as reports of other authors suggest that genetic instability resulting from defective human DNA mismatch repair mechanism in human carcinomas may cause interpretation difficulty during forensic genotyping and DNA profile matching [31][32][33]. We suggest that during genotyping human DNA extracted from histopathological tissue sections caution should be taken when non-match or exclusion based on few discrepancies is concluded.…”

Molecular characterization of commonly used cell lines for bone tumor research: A trans‐European EuroBoNet effort

“…Another interesting finding is the occurrence of additional small alleles of the STRs VWA and D5S818 in HOS-143B, which are absent in HOS, HOS-MNNG and also in the subclones deposited at the ATCC database. Since at least the tetranucleotide repeat VWA was already shown to be frequently involved in microsatellite instability in gastric cancer (Pelotti et al, 2007), we hypothesize that some of the additional alleles in HOS-143B are related to length alterations in their microsatellite sequences.…”

The Changing Spectrum of DNA-Based Specimen Provenance Testing in Surgical Pathology

“…The series documents that STR-based typing can be applied in routine surgical pathology practice in which confirmation of specimen provenance is required, including tissue sections from FFPE tissue blocks, tissue microdissected from routinely prepared H&E-stained tissue slides, tissue microdissected from frozen section slides, bone marrow core biopsies, and cytology specimens. [4][5][6][7][8][9]14 In specific terms, Table 1 shows that testing was informative in 92% of cases (22/24). Both cases in which testing was not informative occurred when testing was performed to rule out a contaminant; in both cases, test failure was due to the lack of sufficient tissue to generate a marker profile in the putative floater.…”

“…1 The CODIS loci feature extreme polyallelism and widespread distribution of the different alleles across different population groups, characteristics that not only make them useful in forensic settings, but also provide a very high power of discrimination for assigning the provenance of tissue samples in clinical settings. [2][3][4][5][6][7][8][9] The clinical usefulness of STR-based testing using the CODIS loci is enhanced by the ease of testing (several commercial kits for analysis of the CODIS and/ or related loci are available) and the availability of extensive technical resources to support test interpretation (including a large database of allele size distribution, largely generated by the forensic community).…”