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

The aim of this study was assessment of possible effects of loss of heterozygosity on human genetic identification of histolopathogical tissue sections. DNA templates were extracted from tumour tissue specimens excised from oncological patients and from reference blood samples. AmpFlSTR Identifiler PCR Amplification Kit and ABI 310 Genetic Analyzer (Applera) were used to obtain genetic profiles. Frequency of LOH was calculated for respective samples. Fisher's exact test was performed for statistical analysis. Forty-two percent of the 101 cancer cases analysed were found to possess alterations of the microsatellites manifesting with allelic loss. The most frequently altered loci were D3S1358 and D18S51. The alteration was detected in 47% of cases with larynx carcinoma, 44% of cases with uveal melanoma, 60% of cases with cervical cancers, one case of liposarcoma G3 and one case od neurofibrosarcoma. No LOH was found in liposarcoma G1, dermatofibrosarcoma and cystosarcoma protuberans in either primary or recurrent tumours. In benign tumours (lipoma and fibroma) LOH was also absent. During genotyping of DNA extracted from histopathological tissue sections caution should be taken when non-match or exclusion based on few discrepancies is concluded

The rs12526453 Polymorphism in an Intron of the PHACTR1 Gene and Its Association with 5-Year Mortality of Patients with Myocardial Infarction

The rs12526453 (C/G) is a single nucleotide polymorphism in an intron of the PHACTR1 gene (phosphatase and actin regulator 1). The C allele is associated with increased risk of coronary artery disease in an unknown mechanism. We investigated its association with long-term overall mortality in patients with ST-elevation myocardial infarction (STEMI) treated invasively. METHODS: Two independent groups of patients with STEMI were analyzed: a derivation group (n= 638) and a validation one (n=348). Genotyping was performed with the TaqMan method. The analyzed end-point was total long term mortality. Additionally, transcriptomic analysis was performed in mononuclear blood leukocytes from rs12526453 CC monozygotes or G allele carriers. RESULTS: In the study group (mean age 62.3 ± 11.9 years; 24.9% of females, n=159), percentages of CC, CG, and GG genotypes were 45.3% (n=289), 44.7% (n=285), and 10% (n=64), respectively. In the 5-year follow-up 105 patients died (16.46%). CC homozygotes had significantly lower mortality compared to other genotypes: 13.1% (n=38) vs. 18.3% in G-allele carriers (n=67), (p=0.017, Cox`s F test). In the validation group 47 patients died within 3 years (13.5%). We confirmed lower mortality of CC homozygotes: 10.1 % (n=18) vs. 16.95% in G-allele carriers (n=29), (p=0.031, Cox`s F test). Transcriptomic analysis revealed a markedly higher expression of NLRP-2 in CC homozygotes. CONCLUSIONS: The rs12526453 CC homozygotes (previously associated with increased risk of myocardial infarction) showed, in 2 independent samples, better long-term survival. The finding of such high effect size, after appropriate validation, could potentially be translated into clinical practic