The present study suggests that the level of cfDNA can be easily quantified using plasma samples. Thus, level of plasma cfDNA might constitute an important noninvasive diagnostic and prognostic valuable tool in cancer breast patients' management.

Expression of BCR/ABL, a constitutively active tyrosine kinase, is a primary event in the pathogenesis of chronic myeloid leukemia (CML) and Ph-positive acute lymphoblastic leukemia (Ph+ALL). Inhibition of the BCR/ABL kinase activity in the BV173 CML cell line with STI571 resulted in a significant overexpression of a 10-kb novel mRNA, found to be the human ortholog of the murine Bach2, a B-cell-specific transcription factor. The human BACH2 cDNA is >9,120 bp long and includes an open reading frame of 2,526 bp encoding a protein with a basic leucine zipper (bZip) and a BTB/POZ domain, mediating DNA-binding and heterodimerization. BACH2 was consistently upregulated (2-10-fold) in all 10 Ph+ lymphoid lines tested following BCR/ABL inhibition. In CML myeloid cell lines (n = 8) and BCR/ABL-negative lines (n = 6), BACH2 was either undetectable by Northern blotting or did not change in response to STI571, suggesting that BACH2 repression by BCR/ABL may be specifically relevant to lymphoid transformation. Quantitative RT/PCR revealed a significantly lower level of BACH2 expression in leukocytes from patients with CML (n = 24) as compared to normal individuals (n = 23) (P < 0.0005). Moreover, CD34+ cells treated in vitro with STI571 exhibited a consistent upregulation of BACH2 in 8 of 10 CMLs but in none of the 9 normal individuals tested. Transcription regulation of BACH2 in BCR/ABL-positive cells was exerted via the MEK pathways, as shown by their responses to the U0126-specific inhibitor. Radiation hybrid mapping and FISH revealed that BACH2 is located on chromosome 6, band q15, a region frequently associated with deletions in ALL and non-Hodgkin's lymphoma, suggesting its possible role as a tumor suppressor gene. However, no rearrangement or loss of signal was observed by Southern blotting in 34 lymphomas, 10 B-cell ALLs, or seven reactive lymph nodes. The pattern of BACH2 expression in BCR/ABL-positive cells suggests that transcriptional repression by this regulator is impaired in CML and may contribute to the emergence of lymphoid blast crisis.

With the objective of identifying candidate tumor suppressor genes, we used fluorescence in situ hybridization to map leukemia-related deletions of the long arm of chromosome 6 (6q). Twenty of 24 deletions overlapped to define a 4.8-Mb region of minimal deletion between markers D6S1510 and D6S1692 within chromosome 6 band q16. Using reverse transcription-PCR, we found evidence of expression in hematopoietic cells for 3 of 15 genes in the region (GRIK2, C6orf111, and CCNC). Comparison between our own and published deletion data singled out GRIK2 as the gene most frequently affected by deletions of 6q in acute lymphocytic leukemia (ALL). Sequence analysis of GRIK2 in 14 ALL cases carrying heterozygous 6q deletions revealed a constitutional and paternally inherited C to G substitution in exon 6 encoding for an amino acid change in one patient. The substitution was absent among 232 normal alleles tested, leaving open the possibility that heterozygous carriers of such mutations may be susceptible to ALL. Although low in all normal hematopoietic tissues, quantitative reverse transcription-PCR showed higher baseline GRIK2 expression in thymus and T cells than other lineages. Among T-cell ALL patients, 6q deletion was associated with a statistically significant reduction in GRIK2 expression (P ‫؍‬ 0.0001). By contrast, elevated GRIK2 expression was measured in the myelomonocytic line THP-1 and in one patient with common ALL. Finally, we detected significant levels of GRIK2 expression in prostate, kidney, trachea, and lung, raising the possibility that this gene may be protective against multiple tumor types.

The distribution of XRCC1Arg 339Gln genotypes showed a significant difference between patients and controls (p=0.025). The presence of at least one XRCC1 399Gln allele indicated an increased risk of AML and the proportion of AML patients homozygous for the Gln/Gln allele was significantly higher than in the control group (p=0.025). However, distributions of the XRCC3 Thr241Met, XPD Lys751Gln, and NQO1Pro 187Ser genotypes were not significantly different between patients and controls. Combined analysis of the studied DNA repair gene polymorphisms did not show an interaction with the detoxification NQO1 Pro187Ser polymorphism.

Background: MicroRNAs (miRNAs) are short noncoding RNAs of ~21 to 23 nucleotides in length that post-transcriptionally regulate mRNA expression. Highthroughput methodologies have shown deregulated miRNA expression in an increasing number of human cancers. MiRNA expression patterns have been found to distinguish tumors of different developmental origin, even better than traditional mRNA expression profiling. Aim: To assess the plasma level of micro-RNA-92a in adult acute myeloid leukemia and to correlate it with prognostic factors and therapeutic response. Patients and Methods: This study was carried out on fifty AML patients as well as fifty healthy subjects as control. Conventional cytogenetics was performed on patients group only while measurement of the plasma level of miRNA-92a using TaqMan quantitative RT-PCR with miRNA-638 as endogenous reference for standardization and FLT3/ITD mutation was performed on patients and controls. Results: The differences in the ratio or relative quantitation (RQ) of plasma miRNa-92a to miRNA-638 in patients group to the control group have confirmed statistical significance. Also there was significant negative correlation between RQ of miRNA-92a and white blood count in patient group. Patients who achieved a response after induction chemotherapy had a mean RQ of miRNA-92a higher than non-responder with statistical significance. With regard to cytogenetics, favorable risk cytogenetics had meant RQ of miRNA-92a that was comparable to intermediate risk cytogenetics. While poor risk cytogenetics had a mean RQ which is significantly lower than both favorable and intermediate risk cytogenetics. Summary/Conclusions: Our data suggest the potential importance of the microRNA-92a as noninvasive cancer biomarkers helping in diagnosis, clinical prediction and therapeutic response.

No abstract

Prostate cancer is a common disease with a multifactorial and complex etiology. It is the most common male malignancy and the second leading cause of death in many countries. The widespread use of PSA testing has increased the detection of this cancer at earlier stages, although this diagnostic method has proved to be insufficient to identify the disease. DNA in most cells is regularly damaged by endogenous and exogenous mutagens. At least four main partially overlapping damage repair pathways operate in mammals. Common polymorphisms in DNA repair genes may alter protein function and an individual's capacity to repair damaged DNA; deficits in repair capacity may lead to genetic instability and carcinogenesis. In the present study, we investigated the genotypic distribution of XRCC1 and XPC polymorphisms and its association with prostate cancer risk, pathological staging and Gleason's scoring. The present study was conducted in the departments of Clinical Pathology, Pathology, and Urology Faculty of Medicine, Alexandria University-Egypt. A total number of 50 patients with pathologically confirmed prostate cancer and 50 age-matched control subjects were enrolled in this study. The diagnosis was made on the basis of histopathological findings, following radical prostatectomy or transurethral resection of the prostate (TURP). Genomic DNA was extracted from peripheral blood using QIAamp blood DNA isolation kits. PCR followed by enzymatic digestion of the PCR products for (XRCC1, XPC) was used for the genotyping of these polymorphisms. Statistical analyses were performed using SPSS statistics version 20. The genotype frequencies of the studied polymorphisms in all the samples (n = 100), PC patients (n = 50) and healthy controls (n = 50) were consistent with the Hardy-Weinberg equilibrium distribution (p-value > 0.05). There was no statistical difference in the genotypes of the XRCC1 Arg399Gln and XPC Lys939Gln between cases and controls. The "Gln" allele frequency of XPC Lys939Gln as well as the "Gln" allele frequency of XRCC1 Arg399Gln tended to be lower in controls than in PC patients. Yet, these decreases were not statistically significant. We also examined the combined effect of XPC and XRCC1 and we found a decreased PC risk when XPC 939 Lys/Lys + Lys/Gln and XRCC1 399 Arg/Arg + Arg/Gln are combined (OR = 0.370, 95% CI = 0.142-0.962).

Chromosome anomalies were suggested to be more frequent in infertile males so our case-control study aimed at evaluating the incidence of spermatic aneuploidies in forty males with severe oligoasthenoteratozoospermia (OAT) and comparing it with that in another forty males having normal semen parameters. Semen samples were collected and analysed in the Clinical Pathology Department according to criteria of the World Health Organization (WHO laboratory manual for the examination and processing of human semen, 2010, WHO Press). Fluorescence in situ hybridisation (FISH) was performed on decondensed spermatozoa from fresh semen ejaculates, using dual coloured chromosome-specific DNA probes labelled with fluorochromes to study sperm aneuploidies in chromosomes 13, 21, X and Y. There was no statistical significant difference between cases and controls regarding disomy frequencies for chromosomes 13, 21 or both combined. However, 13, 21 diploidy frequency was significantly higher among OAT cases. Regarding chromosomes X and Y, both cases and controls showed similar results for disomy/diploidy frequency for both chromosomes; however, there was a statistical significant increase in YY disomy/diploidy frequency among OAT patients. X chromosome-bearing spermatozoa were found to be significantly higher among controls. Patients with severe OAT have a higher total sperm aneuploidy rate, regarding chromosomes 13, 21, X and Y but without a statistical significant difference.