Single nucleotide polymorphisms of XRCC3 gene in hepatocellular carcinoma - relationship with clinicopathological features.

Recent studies support the involvement of XRCC3 gene polymorphisms in carcinogenesis. Our study focuses on the identification of polymorphic variants of XRCC3 in hepatocellular carcinoma (HCC) and an analysis of the relationship between these polymorphic variants and clinicopathological (including the genotype specific risk) and survival characteristics. Fifty cases of HCC were genotyped using molecular biology techniques for Thr241Met, rs861539 (c.722C>T) and 5'-UTR, rs1799796 (c.562-14A>G) polymorphisms. Statistical analysis was based on 2, Fisher's, logistic regression (odd ratio - OR), and log-rank tests. Statistically significant differences were shown only for rs1799796 A>G and tumour grade, between wild type (AA) and heterozygote (AG) genotypes, and wild type (AA) and heterozygote & homozygote (AG & GG) genotypes. The logistic regression analysis found an OR of rs1799796 polymorphism occurrence in HCC related to tumour grade. The statistical analysis revealed, for the rs861539 C>T polymorphism, a better survival only for the homozygote genotype (TT) compared to the heterozygote (CT), and for rs1799796 A>G polymorphism, a longer survival for the wild type (AA) compared to heterozygote (AG) and to heterozygote & homozygote (AG & GG) genotypes, respectively. Our results suggest that XRCC3 gene SNPs could influence the tumour aggressiveness expressed by tumour grade.

Basic aspects in selecting a suitable transgenic rodent model for Alzheimer's disease.

Due to Alzheimer's disease (AD) great aggressiveness, many worldwide health associations began to globalize research efforts in order to find a suitable treatment and to clarify once and for all its controversial aetiology. Moreover, the animal modelling research is one of the best tools to evaluate molecular mechanisms and to correlate them with clinical features and behaviours. However, in order to provide valuable scientific data correlated to low error sources, a rigorous algorithm of selecting the proper animal model for testing is required. An ideal animal model for AD research has probably not yet been developed, but by a careful selection of the existent models or even by developing new models suitable to research conditions, consistent progress in this area of research can be achieved. This paper aims to show and centralize some of the valuable information gathered along the past years of failure and success in Alzheimer's disease animal modelling, in order to provide a theoretical ground for new and innovative aspects in this rather new area of research.

Heterogeneous Distribution of Fetal Microchimerism in Local Breast Cancer Environment.

Fetal cells enter maternal circulation during pregnancy and persist in the woman's body for decades, achieving a form of physiological microchimerism. These cells were also evidenced in tumors. We investigated the frequency and concentration of fetal microchimerism in the local breast cancer environment. From 19 patients with confirmed breast neoplasia, after breast surgical resection, we collected three fresh specimens from the tumor core, breast tissue at tumor periphery, and adjacent normal breast tissue. The presence of male DNA was analyzed with a quantitative PCR assay for the sex determining region gene (SRY) gene. In the group of women who had given birth to at least one son, we detected fetal microchimerism in 100% of samples from tumors and their periphery and in 64% (9 of 14) of those from normal breast tissue. The tissues from the tumor and its periphery carry a significantly increased number of SRY copies compared to its neighboring common breast tissue (p = 0.005). The median of the normalized SRY-signal was about 77 (range, 3.2-21467) and 14-fold (range, 1.3-2690) greater in the tumor and respectively in the periphery than in the normal breast tissue. In addition, the relative expression of the SRY gene had a median 5.5 times larger in the tumor than in its periphery (range, 1.1-389.4). We found a heterogeneous distribution of fetal microchimerism in breast cancer environment. In women with sons, breast neoplasia harbors male cells at significantly higher levels than in peripheral and normal breast tissue.

BRCA1 5382insC founder mutation has not a significative recurrent presence in Northeastern Romanian cancer patients.

Developed two decades ago, oncogenetic medical practice mainly concern breast, ovarian and colorectal cancers, and is targeting the hereditary risk factor, the only one that shows positive predictive value justifying the molecular diagnosis. Screening for BRCA1 and BRCA2 gene mutations is standard practice today for hereditary breast and ovarian cancer (HBOC) families in developed countries, offering the possibility of medical follow-up. The gold standard for molecular diagnosis is Sanger sequencing of all exons and exon-intron boundaries, which is expensive and time consuming. More than 3000 BRCA sequence variants are reported in international databases, but in some populations or ethnic groups a few founder mutations showed to have a recurrent presence. This may be very useful in establishing a combined technical approach for mutation detection, including rapid and cheap pre-screening methods for most common mutations. The BRCA1 5382insC mutation has an Ashkenazi founder effect and is also the second most recurrent mutation in Eastern European populations, having been already identified in several Romanian HBOC patients. Here we present a complete screening of consecutive series of breast and ovarian cancer patients for the presence of BRCA1 5382insC. The presence of the mutation was investigated by allele specific multiplex-PCR on genomic DNA extracted from peripheral blood. No mutation carrier was identified among breast or ovarian cancer patients. Our findings suggest that BRCA1 5382insC may not have a strong recurrent effect in Romanian population comparing to neighboring countries. This may be particularly useful in establishing further pre-screening strategies.

Complete BRCA mutation screening in breast and ovarian cancer predisposition families from a North-Eastern Romanian population.

Breast cancer is the most common cancer in women worldwide, including Romania, where its incidence has increased significantly during the last decade. Ovarian cancer is the fourth leading cause of mortality by cancer in women. BRCA1 and BRCA2 are major cancer predisposition genes, responsible for a large percentage of hereditary breast and ovarian cancer (HBOC) families. We investigated 17 patients from unrelated HBOC families in north-eastern Romania, screening for mutations in BRCA1 and BRCA2 by mutation-specific PCR and by dideoxy sequencing. We identified four BRCA1 and two BRCA2 mutations in the 17 families. The overall mutation frequency was 41% (7/17; 5 BRCA1 and 2 BRCA2). Two mutations (BRCA1 c.2241dupC and BRCA2 c.8680C>T) were novel and not listed in the BIC database. Two recurrent BRCA1 mutations (c.5266dupC and c.181T>G), previously described among Ashkenazi Jewish and Eastern European populations, were also found. Two unclassified variants (UV) were found, one of which was novel (BRCA2 c.4589A>G). Medical follow-up for mutation carriers was implemented. Our study is the first molecular investigation of the role of the BRCA genes in breast and ovarian cancer in Romania.