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. 2009 Jun;50(3):218-27.
doi: 10.3325/cmj.2009.50.218.

Malignant tumors and forensics--dilemmas and proposals

Zoran Budimlija  1 , Connie Lu, Grace Axler-DiPerte, Jessica Seifarth, Dorota Popiolek, Franz Fogt, Mechthild Prinz
Affiliations

Malignant tumors and forensics--dilemmas and proposals

Zoran Budimlija et al. Croat Med J. 2009 Jun.

Abstract

Aim: To evaluate the effect of genetic instability and degradation in archived histology samples from cancerous tumors and to investigate the validity of short tandem repeat (STR) typing of these samples and its potential effect on human identification.

Methods: Two hundred and twenty eight slides of archival pathology tissues from 13 different types of malignant tumors were compared with healthy tissues from the same individuals. DNA analysis was performed using standard techniques for forensic STR analysis, PowerPlex16 and Identifiler on 2 distinct sample sets. Genetic instability was assessed by comparing reference tissues with cancerous tissues derived from the same individual. Loss of heterozygosity, a > or =50% reduction in heterozygosity ratio between healthy and diseased samples, and microsatellite instability, the presence of an additional allele not present in reference tissue, were assessed. The quality of profiles obtained with respect to completeness among the archived samples and degradation using the 2 platforms were also compared.

Results: Profiles obtained using the Identifiler system were generally more complete, but showed 3-fold higher levels of instability (86%) than those obtained using PowerPlex 16 (27%). Instances of genetic instability were distributed throughout all loci in both multiplex STR systems.

Conclusion: After having compared 2 widely used forensic chemistries, we suggest individual validation of each kit for use with samples likely to exhibit instability combined with fixation induced degradation or artifact. A "one size fits all" approach for interpretation of these samples among commercially available multiplexes is not recommended.

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Figures

Figure 1
Figure 1
Correlation between loci obtained using PowerPlex®16 Multiplex STR system and sample age. Each data point shows the percentage of loci obtained (y-axis) for all samples of a specific age (x-axis). A linear negative correlation (R = 0.92) exists between sample age and amplification success.
Figure 2
Figure 2
Correlation between loci obtained using Identifiler® Multiplex STR system and sample age. Each data point shows the percentage of loci obtained (y-axis) for all samples of a specific age (x-axis). Very weak linear correlation (R = 0.83) existed between sample age and profile quality in the Identifiler® system.
Figure 3
Figure 3
Percentage of loci obtained for healthy and tumor profiles using PowerPlex®16 Multiplex STR system. The percentage of loci obtained is shown as a function of the locus and is arranged in size order from the largest to the smallest by dye line (blue, green, yellow). Dark gray bars represent percentages for healthy tissue profiles and open bars represent percentages for malignant tissue profiles.
Figure 4
Figure 4
Percentage of loci obtained for profiles using Identifiler® Multiplex STR system. The percentage of loci obtained is shown as a function of the locus and is arranged in size order from the largest to the smallest by dye line (blue, green, yellow, red). Bars represent all tissue samples (both healthy and tumor) analyzed in Identifiler® Multiplex STR system.
Figure 5
Figure 5
Comparison between percentages of loci obtained for all profiles amplified in Identifiler® Multiplex STR system (closed bars) vs PowerPlex®16 Multiplex STR system (open bars). The percentage of loci obtained is shown as a function of the locus and is arranged in size order from the largest to the smallest by dye line (blue, green, yellow, red). Loci not represented in a particular kit are not shown.
Figure 6
Figure 6
Example of microsatellite instability – the presence of an additional allele not found in the healthy reference (shown in boxed area). The electropherogram represents a sample amplified in PowerPlex®16 and separated on ABI Prism® 3130 Genetic Analyzer. Top line represents the healthy sample with corresponding tumor shown below. Peaks are labeled with allele call, size in base pairs, and height in relative fluorescent units.
Figure 7
Figure 7
Example of microsatellite instability – a size shift in an allele present in the healthy reference (shown in boxed area). Electropherogram represents a sample amplified in PowerPlex®16 and separated on ABI Prism® 3130 Genetic Analyzer. Top line represents the healthy sample with corresponding tumor shown below. Peaks are labeled with allele call, size in base pairs, and height in relative fluorescent units.
Figure 8
Figure 8
Example of partial loss of heterozygosity (shown in boxed area). Electropherogram represents a sample amplified in PowerPlex®16 and separated on ABI Prism® 3130 Genetic Analyzer. Top line represents the healthy sample with corresponding tumor shown below. Peaks are labeled with allele call, size in base pairs, and height in relative fluorescent units.
Figure 9
Figure 9
Example of complete loss of heterozygosity (shown in boxed area). Electropherogram represents a sample amplified in PowerPlex®16 and separated on ABI Prism® 3130 Genetic Analyzer. Top line represents the healthy sample with corresponding tumor shown below. Peaks are labeled with allele call, size in base pairs, and height in relative fluorescent units.
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References

    1. Alonso A, Alves C, Suarez-Mier MP, Albarran C, Pereira L, Fernandez de Simon L, et al. Mitochondrial DNA haplotyping revealed the presence of mixed up benign and neoplastic tissue sections from two individuals on the same prostatic biopsy slide. J Clin Pathol. 2005;58:83–6. doi: 10.1136/jcp.2004.017673. - DOI - PMC - PubMed
    1. Popiolek DA, Prinz MK, West AB, Nazzaruolo BL, Estacio SM, Budimlija ZM. Multiplex DNA short tandem repeat analysis. A useful method for determining the provenance of minute fragments of formalin-fixed, paraffin-embedded tissue. Am J Clin Pathol. 2003;120:746–51. doi: 10.1309/MGW2XKFT0NYQCUHW. - DOI - PubMed
    1. Rubocki RJ, Duffy KJ, Shepard KL, McCue BJ, Shepherd SJ, Wisecarver JL. Loss of heterozygosity detected in a short tandem repeat (STR) locus commonly used for human DNA identification. J Forensic Sci. 2000;45:1087–9. - PubMed
    1. Schwark T, Bachmann C, von Wurmb-Schwark N. STR typing of ductal adenocarcinomas of the pancreas and healthy control tissue in 18 individuals. Leg Med (Tokyo) 2004;6:170–3. - PubMed
    1. Vauhkonen H, Hedman M, Vauhkonen M, Kataja M, Sipponen P, Sajantila A. Evaluation of gastrointestinal cancer tissues as a source of genetic information for forensic investigations by using STRs. Forensic Sci Int. 2004;139:159–67. doi: 10.1016/j.forsciint.2003.10.016. - DOI - PubMed