Vauhkonen H, Hedman M, Vauhkonen M, Kataja M, Sipponen P, Sajantila A
Laboratory of Forensic Biology, Department of Forensic Medicine, University of Helsinki, P.O. Box 40, Helsinki 00014, Finland.
Forensic Sci Int. 2004 Jan 28;139(2-3):159-67. doi: 10.1016/j.forsciint.2003.10.016.
Malignant tissue samples may sometimes be the only source of biological material for forensic investigations, including identification of individuals or paternity testing. However, in use of such samples, uncertainties due to microsatellite instability (MSI) and loss of heterozygosity (LOH) often associated with neoplasias may be encountered. In this study, we have analysed the applicability of autosomal tetranucleotide short tandem repeat (STR) markers, which are routinely used in forensic analysis, to gain genetic information. MSI and LOH were analysed in 41 surgically removed gastrointestinal cancer specimens and the adjascent non-cancerous tissue marginals. The cancer specimens showed great variability in their genetic phenotypes due to MSI or LOH, with only 32% being microsatellite-stable. Of the 15 autosomal STR loci analysed, only TH01 had no MSI-type alteration in these samples. The loci most frequently affected by MSI were D8S1179, D21S11, D18S51 and D19S433 (MSI in 15-17% of cases). LOH-type alterations were observed at all of the loci, including the amelogenin locus used for sex determination. The highest LOH frequency was found at locus D18S51 (27%). The genetic alterations at the marker loci may indicate false homozygosity or heterozygosity, and false gender may result from erroneous deduction of DNA profiles. Therefore, typing of autosomal STRs from malignant tissues in forensic settings warrants careful interpretation of MSI and LOH results together with microscopic analysis of a tissue specimen. Results by two commercially available and widely used forensic DNA profiling kits used here were comparable.
恶性组织样本有时可能是法医调查中生物材料的唯一来源，包括个体识别或亲子鉴定。然而，在使用此类样本时，可能会遇到由于微卫星不稳定性（MSI）和杂合性缺失（LOH）而产生的不确定性，这些情况通常与肿瘤形成有关。在本研究中，我们分析了常用于法医分析的常染色体四核苷酸短串联重复序列（STR）标记获取遗传信息的适用性。对41例手术切除的胃肠道癌标本及其相邻的癌旁非肿瘤组织边缘进行了MSI和LOH分析。由于MSI或LOH，癌标本的遗传表型表现出很大的变异性，只有32%为微卫星稳定型。在所分析的15个常染色体STR位点中，只有TH01在这些样本中没有MSI型改变。受MSI影响最频繁的位点是D8S1179、D21S11、D18S51和D19S433（在15 - 17%的病例中存在MSI）。在所有位点都观察到了LOH型改变，包括用于性别鉴定的牙釉蛋白位点。在D18S51位点发现了最高的LOH频率（27%）。标记位点的基因改变可能表明错误的纯合性或杂合性，错误的DNA图谱推断可能导致错误的性别判断。因此，在法医环境中对恶性组织进行常染色体STR分型时，需要结合组织标本的显微镜分析仔细解读MSI和LOH结果。这里使用的两种市售且广泛使用的法医DNA分析试剂盒的结果具有可比性。
