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Among the tumour suppressor genes that affect critically cell functions and homeostasis, phosphatase and tensin homolog deleted in chromosome 10 (PTEN- gene locus: 10q21) regulates the PI3K/Akt/mTOR signalling pathway. PTEN is deleted, mutated or epigenetically hypermethylated in a variety of human solid malignancies. Salivary gland carcinomas (SGCs) belong to the head and neck carcinomas (HNCs) super category of solid malignancies. Histo-pathologically, they demonstrate a significant diversity due to a variety of distinct and mixed subtypes. Genetically, they are characterized by a broad spectrum of gene and chromosomal imbalances. Referring specifically to suppressor genes, PTEN deregulation plays a critical role in signaling transduction in the corresponding SGC pre- and malignant epithelia modifying the response rates to potential targeted therapeutic strategies. In the current review, we explored the role of PTEN deregulation mechanisms that are involved in the onset and progression of SGCs. [ABSTRACT FROM AUTHOR]

Background. Wilms' tumor (WT) is one of the most common solid tumors in children with unsatisfactory prognosis, but few molecular prognostic markers have been discovered for it. Many genes are associated with the occurrence and prognosis of WT. This study aimed to explore the key genes and potential molecular mechanisms through bioinformatics and to verify the effects of aquaporin 1 (AQP1) on WT metastasis. Methods. Differentially expressed genes (DEGs) were generated from WT gene expression data sets from the Gene Expression Omnibus (GEO) database. Gene functional enrichment analysis was carried out with the Database for Annotation, Visualization and Integrated Discovery (DAVID). A protein-protein interaction network (PPI) was constructed and visualized by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape software. Minimal Common Oncology Data Elements (MCODE) was used to detect the important modules in the PPI network, and the important nodes (genes) in the PPI module were sorted by CytoHubba. RT-qPCR was performed to validate the expression of the key genes in WT. Wound healing and Transwell assays were used to detect the cell migration and invasion abilities of AQP1-overexpressing cells. Phalloidin-iFlour 488 was used to stain the cytoskeleton to observe how AQP1 overexpression affects cytoskeletal microfilament structure. Results. A total of 73 co-expressed DEGs were chosen for further investigation. The importance of homeostasis and transmembrane transport of ions and water were highlighted by functional analysis. Gene regulatory network and PPI network were predicted. MCODE plug identified two important modules. Finally, top five key genes were identified using CytoHubba, including Renin (REN), nephrosis 2 (NPHS2), Solute Carrier Family 12 Member 3 (SLC12A3), Solute Carrier Family 12 Member 1 (SLC12A1) and AQP1. The five key genes were mainly enriched in cell volume and ion homeostasis. RT-qPCR confirmed the expression of the five key genes in WT. AQP1 was validated to be expressed at significantly lower levels in WT than in normal tissue. AQP1 overexpression significantly reduced the migratory and invasive capacity of Wit- 49 cells, as evidenced by reducing the scratch healing rate and the number of perforated control cells by Wit-49 cells. AQP1 overexpression also reduced the expression of biomarkers of epithelial-mesenchymal transformation, decreased levels of vimentin and N-cadherin and increased expression of E-cadherin, resulting in decreased formation of conspicuous lamellipodial protrusions, characteristic of diminishedWTcell invasion and migration. Conclusion. Our study reveals the key genes of WT. These key genes may provide novel insight for the mechanism and diagnosis of WT. AQP1 overexpression inhibited invasion, migration, EMT, and cytoskeletal rearrangement of WT cells, indicating that AQP1 plays a role in the pathogenesis of WT. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is one of the main blood disorders threatening human health today. This study aimed to examine the expression of BCL-2/adenovirus E1B 19 kDa-interacting protein 3-like (BNIP3L) in patients with MM and explore its mechanisms in silico. Bone marrow samples (n = 36 from patients with MM and n = 12 from healthy donors) were used to conduct BNIP3L expression analysis using immunohistochemistry. Microarray or RNA sequencing data from the Sequence Read Archive, Gene Expression Omnibus, and ArrayExpress databases were used to appraise BNIP3L expression and its prognostic role in patients with MM. The co-expressed genes of BNIP3L were identified for enrichment and protein-protein interaction (PPI) analyses to determine the associated signaling pathways. Immunohistochemistry indicated that BNIP3L expression in bone marrow of patients with MM was significantly lower than that in bone marrow of healthy donors. BNIP3L mRNA expression was also significantly lower in patients with MM than in healthy donors. The overall standard mean difference (SMD) for downregulation of BNIP3L was −0.62 [−1.17, −0.06], and the area under the curve was 0.81 [0.78, 0.85] based on a total of 694 MM cases. The overall survival analysis demonstrated that BNIP3L levels could act as an independent protective indicator of MM patient survival (HR = 0.79). Moreover, 261 co-expressed genes of BNIP3L were confirmed and found to be mainly involved in the adipocytokine signaling pathway. We preliminarily proved that downregulation of BNIP3L may play an important role in the occurrence and development of MM, and the promoting cancer capacity may be related to the pathway of adipocytokine signaling pathway. [ABSTRACT FROM AUTHOR]

Construction workers are exposed to a mixture of substances in the workplace considered carcinogenic. This study aimed to characterise gene-specific changes in DNA methylation over the workweek in this population as this type of environmental exposure has not been studied extensively. We evaluated their DNA methylation in 4 gene-promoter regions (CDKN2A, RASSF1A, MLH1 and APC) and 2 repeat elements (ALU and LINE-1) in blood samples obtained on the first and fifth day of the same workweek of a group of 39 male construction workers. DNA methylation was measured by bisulphite-PCR-Pyrosequencing. We also measured the levels of trace elements in the whole blood by ICP-MS. Only the CDKN2A gene had significant differences in the average methylation level between the first and fifth day of the workweek. We also observed that the levels of Cu, Pb, Se, Mn, and Ti decreased during the fifth day of exposure, and only lead, titanium and copper showed a low significant correlation with the methylation level mean for three specific CpG sites of the CDKN2A. In summary, the data suggest that altered levels of CDKN2A methylation in construction workers may be a potential biomarker of recent exposure in this environment. [ABSTRACT FROM AUTHOR]

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BACKGROUND: : Nucleoporin NUP153 (NUP153) is well known to be involved in the regulating of nuclear transport. Although NUP153 is associated with several cancers, its role in colorectal cancer (CRC) and the underlying mechanism are still unknown. OBJECTIVE: The aim of this study was to access the effect of NUP153 on the prognosis of patients with CRC, and cancer cell proliferation. METHODS: The expression levels of NUP153 in CRC tissues and matched normal colon tissues were examined by real-time quantitative PCR and immunohistochemistry. Then the association between NUP153 levels with clinical variables as well as survival time was investigated. Moreover, overexpression of NUP153 in HCT116 cells was established to study its influence on cell proliferation in vitro, and a xenograft model was performed to explore this effect in vivo. RESULTS: We found that NUP153 was highly expressed in adjacent normal tissues than in cancer tissues, and elevated NUP153 expression was negatively associated with pathological grade (P = 0.015), T stage (P = 0.048) and distant metastasis (P = 0.006). Kaplan-Meier analysis revealed that patients with higher NUP153 expression had a longer overall survival (OS) (P = 0.01) and recurrence free disease (RFS) (P = 0.001). Logistic regression analysis further identified NUP153 as an independent prognostic safe factor for OS and recurrence. Moreover, NUP153 overexpression suppressed CRC cells proliferation and inhibited tumor growth in a xenograft model. Its mechanistic investigations showed that NUP153 overexpression inhibited β -catenin transcriptional activity and down-regulated the mRNA expression levels of Wnt downstream proteins-Axin2, cyclinD1, c-myc and lef-1. CONCLUSIONS: NUP153 might be a promising prognostic factor, a potential tumor suppressor and therapeutic target in human CRC through an interaction with the Wnt/ β -catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Expression of E74-like factor 5 (ELF5) in endometrial carcinoma tissues and its clinical significance were investigated. Eighty-four endometrial carcinoma tissues, 30 cases of atypical hyperplasia of endometrium and 30 cases of normal endometrial tissues were selected. Immunohistochemical method was utilized to detect the expression of ELF5 in different endometrial tissues. Moreover, its correlation with clinical pathological indexes of patients with endometrial carcinoma was analyzed. The postoperative follow-up was conducted in all the patients with endometrial carcinoma until June 30th, 2017. The Kaplan-Meier method was used for survival analysis so as to analyze the association of ELF5 expression level with clinical pathological indexes; Cox's proportional hazards regression model was utilized for univariate and multivariate analyses to screen independent risk factors for prognosis of endometrial carcinoma. In normal endometrial tissues, atypical hyperplasia and endometrial carcinoma tissues, the positive expression rates of ELF5 showed a decreased tendency (P=0.016). The positive expression rate of ELF5 in endometrial carcinoma tissues was lower in comparison to normal endometrial tissues (P=0.016). The expression of ELF5 was in accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging of endometrial carcinoma (P<0.05), pathological grading (P<0.05), pathological typing (P=0.001), state of lymph node metastasis (P<0.05) and depth of myometrial invasion (P<0.05). Kaplan-Meier method for survival analysis showed that the average survival time of patients with negative ELF5 expression was shorter in comparison to the patients with positive expression (P=0.004). FIGO staging (P=0.004), pathological grading (P=0.048), depth of myometrial invasion (P=0.024) and lymph node metastasis (P=0.020) were related to the prognosis of patients with endometrial carcinoma, The univariate Cox's regression model analysis indicated that FIGO staging (P=0.010), pathological grading (P=0.040), depth of myometrial invasion (P=0.037), lymph node metastasis (P=0.029) and ELF5 (P=0.010) were associated with the prognosis of patients with endometrial carcinoma. Further, multivariate analysis revealed that ELF5 was an independent risk factor for prognosis of patients with endometrial carcinoma (P=0.035). The expression of ELF5 has a correlation with the occurrence, development and prognosis of endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Genetic conflict theory predicts strong selection for host nuclear factors suppressing endosymbiont effects on reproduction; however, evidence of these suppressors is currently scarce. This can either be caused by a low suppressor evolution rate, or if suppressors originate frequently, by rapid spread and concurrent masking of their activity by silencing the endosymbiont effect. To explore this, we use two populations of a dwarf spider with a similar female bias, caused by a Wolbachia infection. Using inter- and intrapopulation crosses, we determine that one of these populations demonstrates a higher suppressing capability towards Wolbachia despite having a similar population sex ratio. This suggests that spider and endosymbiont are locked in so-called red queen dynamics where, despite continuous coevolution, average fitness remains the same, hence hiding the presence of the suppressor. Finding different suppressor activity in populations that even lack phenotypic differentiation (i.e. similar sex ratio) further supports the hypothesis that suppressors originate often, but are often hidden by their own mode of action by countering endosymbiont effects. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between F box/WD-40 domain protein 7 (FBXW7) and cervical squamous cancer. Methods: We investigated the FBXW7 expression in 136 cervical squamous carcinoma cases through immunohistochemistry and Western-blot analysis to evaluate the clinical significance of FBXW7 and to elucidate the relationship of FBXW7 expression with progression-free survival (PFS) and overall survival (OS). Results: Low FBXW7 expression was associated with high histologic grade, lymphovascular space invasion and lymph node metastasis, among other parameters. Patients with low FBXW7 expression exhibited poor OS and PFS. Conclusions: FBXW7 is related to the susceptibility and prognosis of cervical squamous carcinoma, indicating FBXW7 may be a potentially important target for the prediction of prognosis. [ABSTRACT FROM PUBLISHER]

Hepatocellular carcinoma (HCC) has a high rate of mortality. Further studies into epigenetic changes in HCC, particularly the abnormal methylation of tumor suppressor genes (TSGs), are required, since these changes may provide novel biomarkers for early screening and diagnosis of HCC. By using methylation-specific polymerase chain reaction (MSP), the present study detected the methylation status in the promoter region of 4 candidate TSGs, GSTP1, P16, RIZ1, and RASSF1A, respectively, in 35 paired HCC and tumor-adjacent liver tissues in addition to 20 normal liver tissues. Their effect on the initiation and progression of HCC was also investigated by analyzing the clinicopathological data. The results of the present study revealed that the methylation level of RIZ1 and GSTP1 genes in HCC was significantly increased compared with that in the adjacent tissues (P<0.01) and the normal liver tissues (P<0.01). The methylation frequency of P16 and RASSF1A genes was not significantly increased compared with that observed in the adjacent tissues (P>0.05) but was significantly increased compared with the normal tissues (P<0.01). In HCC tissues, the methylation frequency of the GSTP1 gene in tumors with capsular invasion was significantly increased compared with that in tumors without capsular invasion (P<0.05). The methylation frequency of P16 gene in hepatitis B surface antigen (HbsAg)-positive HCC patients was significantly increased compared with that in HbsAg-negative patients (P<0.05). The methylation status of RIZ1 and RASSF1A genes was not significantly correlated with the clinicopathological data (P>0.05). Previous studies have demonstrated that the methylation status of RIZ1 and GSTP1 genes is HCC-specific, and thus may be used as a biomarker to assist the clinical diagnosis of HCC. While the methylation of GSTP1 gene promoter may associate with the invasiveness of HCC, chronic hepatitis B virus infection may be the cause of methylation-induced P16 inactivation. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is considered a serious public health problem in many countries. Recently, genetic variations have been considered as important factors to cancer susceptibility and prognosis. More specifically, genetic polymorphisms have been associated with the development and prognosis of HNSCC. The purpose of the current study was to investigate an association among p16 gene polymorphism at rs11515, age, and HNSCC aggressiveness. PCR-RFLP analysis was used to investigate the p16 gene in 96 patients with HNSCC and in 100 individuals without HNSCC. A case group was categorized by age in younger (<60 years) and older (≥60 years) patients. Differences between the case and control groups were determined using Fisher and chi-squared tests. Time of survival was calculated from the date of diagnosis to the date of last follow-up visit or to the date of death using the Kaplan-Meier estimator and comparing this to the log-rank test. Statistical significance was set at p < 0.05. In the present study, no association was established between HNSCC and rs11515 polymorphism, as indicated in a previous study. We found that HNSCC individuals with large-sized tumors and with metastatic disease presented worse overall survival, consistent with fundamental concepts that establish the effects of tumor size and lymph node metastasis to HNSCC outcomes. This study identified that there is no difference in the distribution of rs11515 between the control and HNSCC groups. In addition, no differences between rs11515 genotypes and clinicopathological parameters were observed. [ABSTRACT FROM AUTHOR]

Spry2 has been characterized as a negative regulator of the extracellular-regulated kinase (ERK) pathway. In this study we analysed whether epigenetic alterations of hSpry2 promoter occur in human lymphoid/hematopoietic malignancies. Our results revealed that hSpry2 promoter was hypermethylated in the HT cell line derived from a B-cell diffuse lymphoma, which correlated with decreased hSpry2 expression. We detected deregulation of the ERK pathway in these cells, but not in other blood cell lines expressing hSpry2. In addition, the ectopic overexpression of hSpry2 in HT cells drastically reduced the activation of ERK upon phorbol 12-myristate-13-acetate stimulation. Nude mice inoculated with HT mock cells developed tumors seven times larger than those from HT-hSpry2-transfected cells. We found hypermethylation of hSpry2 promoter in 37% (26 cases out of 71) of primary tumors from patients with B-cell diffuse lymphoma but none in normal B lymphocytes from 37 healthy individuals. Finally, we detected that hSpry2 promoter hypermethylation was associated with a significant decrease in the 5-year survival rate. These data suggest that hSpry2 could be important in lymphoid malignancies.Oncogene (2008) 27, 4969–4972; doi:10.1038/onc.2008.129; published online 21 April 2008 [ABSTRACT FROM AUTHOR]

New sources of resistance to crown rust, Puccinia coronata f. sp. avenae (Eriks.), the major fungal disease of cultivated oat, Avena sativa L. (2 n = 6 x = 42), are constantly needed due to frequent, rapid shifts in the virulence pattern of the pathogen. Crown rust resistance identified in the diploid oat A. strigosa (Schreb.) (2 n = 2 x = 14) accession CI6954SP was transferred into cultivated oat using two methods: direct cross of the diploid to a hexaploid cultivar facilitated by embryo rescue, and initial cross of the diploid to a wild tetraploid oat to make a synthetic hexaploid for subsequent crossing to a hexaploid cultivar. Two tetraploids, a crown rust resistant A. murphyi (Ladiz.) accession P12 and a susceptible A. insularis (Ladiz.) accession INS-1, were used in the 2 x·4 x crosses. Resistant backcross-derived lines were recovered by both methods. Although the 2 x·4 x synthetic method did not require the laborious discovery and rescue of an infrequent initial hybrid embryo of the direct cross, the direct cross method provided more rapid backcross recovery of plants with high fertility, full transmission of resistance, and desired plant and seed phenotypes. A suppressor effect, present initially but segregating in backcrosses, appeared to come from the CI6954SP donor and is the same as, or analogous to, suppression by an oat line with the crown rust resistance gene Pc38. No resistance from A. murphyi P12 was detected in advanced generations when it was introduced either as a component of a synthetic hexaploid or in direct crosses to A. sativa, indicating suppression of its resistance in interploidy combinations. That the dominant resistance gene transferred from CI6954SP and a gene Pc94 introgressed earlier from a different A. strigosa accession may be the same or quite similar to one another is indicated by their in-common specificity to suppression of resistance expression, susceptibility to a newly recovered rust isolate, and close linkage to the molecular marker SCAR94-2. The introgressed resistance genes from the different sources, even if the same, may have different cultivar genomic introgression sites, which would allow tests of dosage effects on resistance expression. [ABSTRACT FROM AUTHOR]

miRNAs, their involvement in cancer development and their potential to be robust biomarkers of diagnosis, staging, prognosis and response to therapy are reviewed. In small RNA animal biogenesis, miRNA genes in the nucleus are transcribed to generate long primary transcripts (pri-miRNAs), which are first cropped by RNase-III-type enzyme Drosha to release hairpin intermediates (pre-miRNAs) in the nucleus. Pre-miRNA is then exported to the cytoplasm by exportin-5. Following arrival in the cytoplasm, pre-miRNAs are subjected to the second processing step (dicing) to release the mature miRNA duplex, which is then separated: one strand becomes the mature miRNAand the other is degraded. These tiny miRNAs induce messenger degradation, translational repression or both. However, there is no evidence to demonstrate that these two mechanisms exist in the regulation of the same gene. Since a miRNA can target numerous mRNAs, often in combination with other miRNAs, these miRNAs operate a highly complex regulatory network. The specific function in most mammalian miRNAs is unknown. However, data suggest that miRNA genes, approximately 1% of all human genes, regulate protein production for 20-30% or more of all genes. miRNA expression profiles are effective for classifying solid and hematologic human cancers, and have shown great promise for early cancer detection. This is of great importance for effective treatment before the cells metastasize; therefore, tumors can be surgically resected. Computer-based prediction approaches of miRNAs and their targets, and biological validation techniques for ascertaining these predictions, currently play a central role in the discovery of miRNAs and in elucidating their function. Guidelines have been established for the identification and annotation of new miRNAs to distinguish them from other RNAs, especially siRNAs. These guidelines take into account factors such as transcript structure, conservation and processing, and a centralized, searchable database of all possible miRNA sequence information and annotation for humans and of more than 38 other species. Two approaches are used to characterize miRNAs: studying expression of known miRNAs by hybridization-based techniques (e.g., northern blots, RNase protection, primer extension, real-time, quantitative PCR and microarrays) or discovery of novel miRNAs molecules by cloning and sequencing. Owing to their adaptability and high throughput, microarrays may prove to be the preferred platform for whole-genome miRNA expression analysis. [ABSTRACT FROM AUTHOR]

Mutations in p53 gene exons 5–9 were studied in 44 non-Hodgkin's lymphomas (NHL) consisting of 35 B-NHL and 9 T-NHL. Missense mutations were found in two diffuse large B-cell lymphomas (DLBL) and one peripheral T-cell lymphoma (unspecified). Double transversion missense and nonsense mutations were detected in one DLBL and one adult T-cell leukemia/lymphoma. Silent mutations were found in two DLBL. Detailed histomorphological study showed that cases harboring p53 missense mutation with/without nonsense mutation tended to have larger nuclei with much more prominent nucleoli. Cytomorphometric analysis was therefore conducted by measuring the gross area of 100 lymphoma cell nuclei in 44 cases and the results were compared between lymphomas harboring p53 missense mutation with/without nonsense mutation and lymphomas harboring p53 silent mutation or lacking mutation. It was found that the lymphomas harboring p53 missense mutation with/without nonsense mutation had a highly significantly larger nuclear gross area than lymphomas with silent p53 mutation or lacking mutation (two-sample t-test, P < 0.00001; Exact Wilcoxon rank–sum test, P < 0.00001). This result suggests that p53 mutation might induce enlargement of neoplastic cell nuclei by some molecular mechanism. [ABSTRACT FROM AUTHOR]

Rs1046AB is a line which is true breeding for a dominant genetic male sterility gene ( Ms) but which is a mixture of male fertile and sterile individuals (a two-type line) because it is segregating for a dominant suppressor gene ( Rf). This system provides a promising alternative to the CMS system for hybrid breeding in Brassica napus. In order to identify molecular markers linked to the rf gene, a near-isogenic line (NIL) population from the cross between a sterile individual ( MsMsrfrf) and a fertile individual ( MsMsRfrf) in Rs1046AB was subjected to amplified fragment length polymorphism (AFLP) analysis, with a combination of comparing near isogenic lines (NILs) and bulked segregant analysis (BSA). From 2,816 pairs of AFLP primers, six fragments showing polymorphism between the fertile and sterile bulks as well as the individuals of the bulks were identified. Linkage analysis indicated that the six AFLP markers are tightly linked to the Rf gene and all are distributed on the same side. The minimum genetic distance between the Rf gene and a marker was 0.7 cM. Since the AFLP markers are not suitable for large-scale application in MAS (marker-assisted selection), our objective was to develop a fast, cheap and reliable PCR-based assay. Consequently, three of the four closest AFLP markers were converted directly to sequence characterized amplified region (SCAR) markers. For the other marker a corresponding SCAR marker was successfully obtained after isolating the adjacent sequences by PCR Walking. The available SCAR markers of the Rf gene will greatly facilitate future breeding programs using dominant GMS to produce hybrid varieties. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate the mechanism of hMLH1 deregulation in non-small cell lung cancer (NSCLC). METHODS A genetic and epigenetic study of the hMLH1 gene was performed using surgical primary tumors from 40 NSCLC patients and their corresponding noncancerous tissues. The molecular alterations examined included promoter methylation by Hpa II/Mpa I- based PCR analysis, loss of heterozygosity (LOH) by D3S1621 locus PCR-electrophoresis-silver staining, as well as the loss of protein expression by immuno-histochemical analysis. RESULTS The frequencies of hypermethylation, LOH and loss of protein expression of hMLH1 were 67.5% (27/40), 65% (26/40) and 72.5% (29/40), respectively. Among 26 hMLH1 gene LOH (+) cases, 21 (80.8%) showed hypermethylation, which was significantly higher than the group of LOH (−). The frequency of the double inactivation of the hMLH1 gene by hypermethylation and LOH related to a loss of protein expression of 72.4% (21/29). CONCLUSION Biallelic inactivation of the hMLH1 gene by hypermethylation and LOH most likely will cause loss of hMLH1 protein expression and play an important role in the development of NSCLC. Therefore, controlling and monitoring for hypermethylation of the hMLH1 gene may be partially useful for treatment and early diagnosis of NSCLC. [ABSTRACT FROM AUTHOR]

DSS1 is an evolutionarily conserved acidic protein that binds to BRCA2. However, study of the function of DSS1 in mammalian cells has been hampered because endogenous DSS1 has not been detectable by Western blotting. Here, we developed a modified Western blotting protocol that detects endogenous DSS1 protein, and used it to study the function of DSS1 and its interaction with BRCA2 in mammalian cells. We found that essentially all BRCA2 in human cell lines is associated with DSS1. Importantly, we found that RNAi knockdown of DSS1 in human cell lines led to dramatic loss of BRCA2 protein, mainly due to its increased degradation. Furthermore, the stability of BRCA2 mutant devoid of the DSS1-binding domain is unaffected by the depletion of DSS1. Most notably, like BRCA2 depletion, DSS1 depletion also led to hypersensitivity to DNA damage. These results demonstrated that the stability of BRCA2 protein in mammalian cells depends on the presence of DSS1. Deletion or mutation of DSS1 or suppression of its expression by other mechanisms are therefore potential causative mechanisms for human breast and ovarian cancer. Such mechanisms may be relevant to sporadic as well as familiar breast cancer where BRCA1 and BRCA2 mutations are not present.Oncogene (2006) 25, 1186–1194. doi:10.1038/sj.onc.1209153; published online 3 October 2005 [ABSTRACT FROM AUTHOR]

Objective: To detect the aberrant methylation patterns in the CpG islands of p16 and p15 tumor suppressor genes, and to analyze its correlation with pancreatic carcinogenesis and with clinicopathological characteristics of patients with pancreatic cancer (PC). Methods: The methylation-specific polymerase chain reaction (MSP) method was used to monitor methylation patterns in the CpG islands of p15 and p16 genes from 29 cases of PC and 3 cases of chronic pancreatitis (CP) paraffin-embedded tissue, as well as 2 cases of normal liver tissues and 12 cases of normal blood samples. Results: p15 and p16 genes were detected to show unmethylation patterns and no amplification using methylation-specific primers in control group. The aberrant methylation rates of p16 in carcinoma tissue and adjacent noncarcinoma tissue were 37.9% (11 of 29 cases) and 34.5% (10 of 29 cases) respectively. Of the 11 aberrant methylated samples, 5 showed complete methylation and 6 hemimethylation. The methylation rates of p15 gene in carcinoma tissue and adjacent noncarcinoma tissue were 27.5% (8/29) and 24.4% (7/29) respectively. Of the 8 aberrant methylated samples, 3 showed complete methylation and 5 hemimethylation. In 6 PC samples, aberrant methylation in CpG islands of both p15 and p16 genes existed simultaneously. The aberrant methylation patterns in CpG islands of p15 and p16 genes had no close correlation with the clinicopathological characteristics (age, sex, smoking, volume of primary tumor, differentiation, clinical stage and histological classification) of the patients with PC (P>0.05). Conclusion: The aberrant methylation in CpG islands of p15 and p16 genes could be regarded as an early molecular event in PC and had no close correlation with the clinicopathological characteristics of the patients with PC. [ABSTRACT FROM AUTHOR]

The interest in oligodendrogliomas has increased since it became evident that a subset of these tumors respond to chemotherapy or radiation. This interest was augmented when the combined loss of the short arm of chromosome 1 and the long arm of chromosome 19 was identified as a powerful prediction factor for response. Lack of stringent morphological criteria allow high-interobserver variation with regard to classification and grading of oligodendroglial tumors. The prospect of beneficial chemotherapy prompted neuropathologists to diagnose more 'oligodendroglioma' than before. Therefore, there is great demand for unambiguous classification of oligodendroglial tumors. Supplementary analysis of the integrity of chromosomal arms 1p and 19q may greatly assist diagnostic characterization of tumors with oligodendroglial phenotype. The underlying mechanisms for these deletions are not known. Tumor suppressor genes on 1p and 19q relevant for oligodendroglioma have not yet been identified. Knowledge of these genes and the mechanisms of their inactivation might help to understand why oligodendroglial tumors do respond better to chemotherapy and radiotherapy than astrocytomas. This review compiles clinical, pathological and molecular genetic findings on oligodendrogliomas and oligoastrocytomas of WHO Grades II and III to present a brief overview on recent developments. [ABSTRACT FROM AUTHOR]

The prognostic value of cytosolic p53 protein was evaluated in 458 operable breast carcinomas by immunoblotting using the monoclonal antibody PAb 1801. Two hundred and five carcinomas (45%) showed positive p53 accumulation and 55% were p53 negative. When comparing p53 positivity and other clinicopathological parameters, significant differences were found with younger age (p = 0.017), premenopausal status (p = 0.003), increasing tumor size (p = 0.026), negative estrogen receptor (p = 0.003) and negative progesterone receptor (p = 0.047), but not with histologic grade, axillary lymph node status, stage or erbB-2 expression. With a median follow-up of 34 months (range 3-70), relapse has occurred in 73 patients. Disease-free survival curves showed that patients with p53-positive tumors had a significantly shorter disease-free survival than patients with p53-negative carcinomas (log-rank test, p = 0.027). A multivariate analysis of disease-free survival showed that p53, tumor size, histologic grade and progesterone receptor had significant independent prognostic value. The immunoblotting technique was controlled with p53 immunohistochemistry in 94 paired samples. We obtained a statistically significant correlation (p = 0.0004) between the two methods. Our results show that the immunoblotting technique offers an alternative approach in evaluating the p53 status of breast biopsy material using cytosolic extracts, and confirm that p53 accumulation is a significant independent indicator of a poor prognosis in operable breast carcinoma. Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A cell line designated CUMO-2 has been established from an undifferentiated ovarian carcinoma. The s.c. injection of cells into nude mice gave rise to fast-growing tumors, while the i.p. route induced a peritoneal carcinomatosis with ascites. Histopathologically, the transplanted s.c. tumors closely resembled the original tumor, but tumors developed in the peritoneal cavity were highly anaplastic. The epithelial nature of the cells was confirmed by ultrastructural analysis. Sequential cytogenetic analyses on early and late passages revealed highly aneuploid tumor cells with consistent structural aberrations of chromosomes 1, 3, 8 and 11. CUMO-2 cells were found to produce CA 125 in vitro and in vivo. Cytosol estrogen receptor (ER) was found but progesterone receptor (PR) was not measured. HLA typing indicated the presence of DR8 and DQw4. A gonadotropin-releasing hormone (Gn-RH) analog inhibited cell growth and Gn-RH receptor mRNA was detected by reverse transcription/polymerase chain reaction in this cell line. Administration of transforming growth factor β1 inhibited both cell growth and c- myc mRNA expression. This cell line demonstrated a conformational band shift in exon 7 of the p53 gene. It was a frameshift mutation. [ABSTRACT FROM AUTHOR]

Cigarette smoking and certain types of occupational exposure to arylamines appear to be the main cause of human urinary bladder cancer. Little is known of the promotion of bladder cancer in humans, although this stage has been demonstrated in rodents. Perhaps as a consequence of initiation, multifactorial alterations of cellular genes occur. These genes include the epidermal growth factor receptor gene, erbB-2, int-2, hst, and H- ras, which exert positive control over cell growth, as well as the suppressor genes Rb-1, and the gene coding for p53. Chromosomal changes such as deletions, translocations and/or amplifications related to these genes may be of significance for prognosis of this disease. [ABSTRACT FROM AUTHOR]

The chromosomal location of a suppressor for the powdery mildew resistance genes Pm8 and Pm17 was determined by a monosomic set of the wheat cultivar Caribo. This cultivar carries a suppressor gene inhibiting the expression of Pm8 in cv Disponent and of Pm17 in line Helami-105. In disease resistance assessments, monosomic F hybrids (2n=41) of Caribo x Disponent and Caribo x Helami-105 lacking chromosome 7D were resistant, whereas monosomic F hybrids involving the other 20 chromosomes, as well as disomic F hybrids (2n=42) of all cross combinations, were susceptible revealing that the suppressor gene for Pm8 and Pm17 is localized on chromosome 7D. It is suggested that genotypes without the suppressor gene be used for the exploitation of genes Pm8 and Pm17 in enhancing powdery mildew resistance in common wheat. [ABSTRACT FROM AUTHOR]

Wild-type and mutant human p53 genes were transfected into the nasopharyngeal carcinoma (NPC) cell line CNE-3. Tumorigenicity in nude mice showed that the tumor resulting from the cells transfected with the wild-type p53 gene grew more slowly and was smaller than that from the cells transfected with mutant p53 gene and that from control CNE-3 cells. In contrast, the tumor from the cells transfected with the mutant p53 gene grew faster than that produced by cells transfected with the wild-type p53 gene and that produced by control CNE-3 cells. The results demonstrate that the wild-type p53 gene could inhibit the NPC cell growth in nude mice and the mutant p53 gene could enhance the NPC cell growth in nude mice. The p53 gene may also play an important role in the pathogenesis of NPC. [ABSTRACT FROM AUTHOR]