Evaluation of allelic alterations in short tandem repeats in different kinds of solid tumors—possible pitfalls in forensic casework

Abstract 

Archival pathology specimens are nowadays a frequently used source in forensic identification or paternity testing, if no other material is available. A greater part of this archived material, however, consists of solid tumors known for aberrations in coding and non-coding regions of the genome. Therefore, alterations of short tandem repeats (STRs) used in forensic casework are also possible. In our study of 118 solid tumors, 46 lymph node metastases, and 16 distant metastases with the AmpFlSTR™ Profiler Plus PCR amplification kit comprising nine STR loci, we detected four kinds of changes between normal and tumor tissue: partial loss of one allele (pLOH), complete loss of one allele (LOH), occurrence of an additional allele and occurrence of a new allele instead of that found in normal tissue. Twenty-two percent of the tumor lesions displayed pLOH, but only in 14% one allele was completely lost. New alleles could be demonstrated in 18% of tumors, and in 8% the new allele in the tumor tissue replaced the one found in normal tissue. The changes were distributed over all nine STRs, but the STRs mostly affected were FGA, D3S1558, D18S51 and D21S11. The occurrence of new alleles in the tetra-nucleotide repeats correlated mainly with microsatellite instability in di-nucleotide and mono-nucleotide repeats. The occurrence of new alleles was most frequent in primary tumors of colon carcinomas and HNSCC metastases. In melanomas, only loss of alleles could be found. Our results demonstrate that the use of tumor tissue in forensic identification and paternity testing is questionable, especially if only tumors with known microsatellite instability are available.

Keywords:  Short tandem repeat (STR), Nuclear microsatellite instability (nMSI), Loss of heterozygosity (LOH), Solid tumors