Verification of microRNA expression in human endometrial adenocarcinoma.

Background: MicroRNAs are small non-coding RNAs that have been implicated in tumor initiation and progression. In a previous study we identified 138 miRNAs as differentially expressed in endometrial adenocarcinoma compared to normal tissues. One of these miRNAs was miRNA-34a, which regulates several genes involved in the Notch pathway, which is frequently altered in endometrial cancer.

Genome-wide discovery of miRNAs using ensembles of machine learning algorithms and logistic regression.

In silico prediction of novel miRNAs from genomic sequences remains a challenging problem. This study presents a genome-wide miRNA discovery software package called GenoScan and evaluates two hairpin classification methods. These methods, one ensemble-based and one using logistic regression were benchmarked along with 15 published methods.

miREC: a database of miRNAs involved in the development of endometrial cancer.

Background: Endometrial cancer (EC) is the most frequently diagnosed gynecological malignancy and the fourth most common cancer diagnosis overall among women. As with many other forms of cancer, it has been shown that certain miRNAs are differentially expressed in EC and these miRNAs are believed to play important roles as regulators of processes involved in the development of the disease. With the rapidly growing number of studies of miRNA expression in EC, there is a need to organize the data, combine the findings from experimental studies of EC with information from various miRNA databases, and make the integrated information easily accessible for the EC research community.

MicroRNA expression in human endometrial adenocarcinoma.

Background: MicroRNAs are small non-coding RNAs that play crucial roles in the pathogenesis of different cancer types. The aim of this study was to identify miRNAs that are differentially expressed in endometrial adenocarcinoma compared to healthy endometrium. These miRNAs can potentially be used to develop a panel for classification and prognosis in order to better predict the progression of the disease and facilitate the choice of treatment strategy.

Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate.

Background: The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate.

Validation of suitable endogenous control genes for quantitative PCR analysis of microRNA gene expression in a rat model of endometrial cancer.

Background: MicroRNAs are small RNA molecules that negatively regulate gene expression by translational inhibition or mRNA cleavage. The discovery that abnormal expression of particular miRNAs contributes to human disease, including cancer, has spurred growing interest in analysing expression profiles of these molecules. Quantitative polymerase chain reaction is frequently used for quantification of miRNA expression due to its sensitivity and specificity.

Expression patterns of Phf5a/PHF5A and Gja1/GJA1 in rat and human endometrial cancer.

Endometrial adenocarcinoma is the most frequently diagnosed cancer of the female genital tract in the western world. Studies of complex diseases can be difficult to perform on human tumor samples due to the high genetic heterogeneity in human. The use of rat models is preferable since rat has similarities in pathogenesis and histopathological properties to that of human.

Classification of tumor samples from expression data using decision trunks.

We present a novel machine learning approach for the classification of cancer samples using expression data. We refer to the method as "decision trunks," since it is loosely based on decision trees, but contains several modifications designed to achieve an algorithm that: (1) produces smaller and more easily interpretable classifiers than decision trees; (2) is more robust in varying application scenarios; and (3) achieves higher classification accuracy. The decision trunk algorithm has been implemented and tested on 26 classification tasks, covering a wide range of cancer forms, experimental methods, and classification scenarios.

The impact of the genetic background on the genome make-up of tumor cells.

Endometrial adenocarcinoma (EAC) is the most common form of malignancy in the female genital tract, ranking as the fourth leading form of invasive tumors that affect women. The BDII inbred rat strain has been used as a powerful tumor model in studies of the genetic background of EAC. Females from the BDII strain are prone to develop tumors with an incidence of more than 90%.

SKY analysis revealed recurrent numerical and structural chromosome changes in BDII rat endometrial carcinomas.

Background: Genomic alterations are common features of cancer cells, and some of these changes are proven to be neoplastic-specific. Such alterations may serve as valuable tools for diagnosis and classification of tumors, prediction of clinical outcome, disease monitoring, and choice of therapy as well as for providing clues to the location of crucial cancer-related genes.Endometrial carcinoma (EC) is the most frequently diagnosed malignancy of the female genital tract, ranking fourth among all invasive tumors affecting women.

A miRNA expression signature that separates between normal and malignant prostate tissues.

Background: MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that post-transcriptionally regulate genes involved in several key biological processes and thus are involved in various diseases, including cancer. In this study we aimed to identify a miRNA expression signature that could be used to separate between normal and malignant prostate tissues.

Results: Nine miRNAs were found to be differentially expressed (p <0.

Loss of glutathione peroxidase 3 expression is correlated with epigenetic mechanisms in endometrial adenocarcinoma.

Glutathione peroxidase 3 (GPX3) is one of the key enzymes in the cellular defense against oxidative stress and the hepatocyte growth factor receptor, (MET) has been suggested to be influenced by the GPX3 gene expression. In a previous microarray study performed by our group, Gpx3 was identified as a potential biomarker for rat endometrial adenocarcinoma (EAC), since the expression was highly downregulated in rat EAC tumors. Herein, we have investigated the mRNA expression and Gpx3 and Met in rat EAC by real time quantitative PCR (qPCR), and the methylation status of Gpx3.

Validation of suitable endogenous control genes for expression studies of miRNA in prostate cancer tissues.

When performing quantitative polymerase chain reaction analysis, there is a need for correction of technical variation between experiments. This correction is most commonly performed by using endogenous control genes, which are stably expressed across samples, as reference genes for normal expression in a specific tissue. In microRNA (miRNA) studies, two types of control genes are commonly used: small nuclear RNAs and small nucleolar RNAs.

Gene expression profiling predicts a three-gene expression signature of endometrial adenocarcinoma in a rat model.

Background: In the Western world, endometrial cancers are the most common gynaecological neoplastic disorders among women. Initial symptoms are often vague and may be confused with several other conditions or disorders. Thus, there is a need for an easy and reliable diagnostic tool.

Rearrangement and allelic imbalance on chromosome 5 leads to homozygous deletions in the CDKN2A/2B tumor suppressor gene region in rat endometrial cancer.

The inbred BDII rat is a valuable experimental model for the genetic analysis of hormone-dependent endometrial adenocarcinoma (EAC). One common aberration detected previously by comparative genomic hybridization in rat EAC is loss affecting mostly the middle part of rat chromosome 5 (RNO5). First, we applied an RNO5-specific painting probe and four region-specific gene probes onto tumor cell metaphases from 21 EACs, and found that rearrangements involving RNO5 were common.

Recurrent chromosome 10 aberrations and Tp53 mutations in rat endometrial adenocarcinomas.

Human genetic heterogeneity and differences in the environment and life style make analysis of complex diseases such as cancer difficult. By using inbred animal strains, the genetic variability can be minimized and the environmental factors can be reasonably controlled. Endometrial adenocarcinoma (EAC) is the most common gynecologic malignancy, ranking fourth in incidence among tumors in women.

Expression analysis of human endometrial adenocarcinoma in an inbred rat model.

Endometrial cancer (EC) is the most abundant female gynaecologic malignancy, ranking fourth in incidence among invasive tumors in women. Hormone-related (estrogen-dependent) EC is the prevalent subtype and accounts for approximately 75% of these cancers. Females of the BDII inbred rat strain are extremely prone to endometrial adenocarcinoma, (EAC) and approximately 90% of virgin females spontaneously develop EAC during their life span.

Altered transforming growth factor-beta pathway expression pattern in rat endometrial cancer.

Endometrial cancer is the most abundant female gynecologic malignancy, ranking fourth in incidence among invasive tumors in women. Females of the BDII inbred rat strain are extremely prone to endometrial adenocarcinoma (EAC), and approximately 90% of virgin females spontaneously develop EAC during their lifetime. Thus, these rats serve as a useful model for the genetic analysis of this malignancy.

Analysis of chromosome 10 aberrations in rat endometrial cancer-evidence for a tumor suppressor locus distal to Tp53.

We have recently shown in the BDII rat model of human endometrial adenocarcinoma (EAC), rat chromosome 10 (RNO10) is frequently involved in chromosomal aberrations. In the present study, we investigated the association between RNO10 deletions, allelic imbalance (AI) at RNO10q24 and Tp53 mutation in 27 rat EAC tumors. We detected chromosomal breakage accompanied by loss of proximal and/or gain of distal parts of RNO10 in approximately 2/3 of the tumors.

Deriving evolutionary tree models of the oncogenesis of endometrial adenocarcinoma.

Endometrial adenocarcinoma (EAC) is the fourth leading cause of cancer death in women worldwide, but not much is known about the underlying genetic factors involved in the development of this complex disease. In the present work, we used 3 different algorithms to derive tree models of EAC oncogenesis from data on the frequencies of genomic alterations in rat chromosome 10 (RNO10). The tumor material was derived from progenies of crosses between the EAC susceptible BDII inbred rat strain and two non susceptible inbred rat strains.

Allelic imbalance on chromosome 10 in rat endometrial adenocarcinomas.

Earlier work using comparative genome hybridization (CGH) has shown that rat chromosome 10 (RNO10) is frequently involved in cytogenetic aberrations in BDII rat endometrial adenocarcinomas (EAC). Relative reduction in copy number (chromosomal deletions) was seen in the proximal to middle part of the chromosome, whereas there were increases in copy number in the distal part. The occurrence of RNO10 aberrations was further analyzed in DNA from primary tumor material from 42 EACs and 3 benign endometrial tumors using allelotyping of microsatellite markers.

RatMap--rat genome tools and data.

The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.

Inconsistent susceptibility to autoimmunity in inbred LEW rats is due to genetic crossbreeding involving segregation of the arthritis-regulating gene Ncf1.

We recently identified a single-nucleotide polymorphism in the Ncf1 gene, a component of the NADPH oxidase complex, to be the cause of one of the strongest identified loci for arthritis severity in rats. This polymorphism was found to be naturally occurring in a collection of inbred rat strains as well as in wild rats. Among the inbred strains we found that different LEW substrains (LEW/Ztm and LEW/Mol), originating from different breeders, showed an allelic discrepancy in Ncf1, suggesting an impact on arthritis susceptibility between these substrains.

Detailed chromosomal and radiation hybrid mapping in the proximal part of rat Chromosome 10 and gene order comparison with mouse and human.

The rat provides valuable and sometimes unique models of human complex diseases. To fully exploit the rat models in biomedical research, it is important to have access to detailed knowledge of the rat genome organization as well as its relation to the human genome. Rat Chromosome 10 (RNO10) harbors several important cancer-related genes.

The functional significance of absence: the chromosomal segment harboring Tp53 is absent from the T55 rat radiation hybrid mapping panel.

The T55 rat radiation hybrid (RH) mapping panel has been reported to retain the entire rat genome at retention frequencies between 22% and 37%. However, we found that a small segment of rat chromosome 10 harboring at least four different genes, including Tp53, was completely absent from the panel (retention frequency = 0%). Two other markers located in the vicinity exhibited much reduced retention (2-6%).