Application Of Dna Microarrays To The Study Of Bladder Cancer

The main advantage of DNA arrays is that they allow the study of the multiple tran-scriptional events that take place when normal urothelium is transformed into tumor tissue in single experiments. Expression profiling using cell lines has been used to gain an insight into the molecular events associated with the disease. An example of how the technology can be applied to the discovery of gene functions and pathways in bladder cancer is provided by the following study. Tumor cell growth...

Experimental Biology Of Prostate Cancer

Several excellent reviews of the molecular biology of prostate cancer are available, and only a few of the more common molecular alterations and their potential significance are highlighted here (4,12). The analysis of chromosomal alterations in cancer has identified many changes reflecting loss or gain of function of particular genes. Consistent allelic loss is expected to reflect the location of putative tumor suppressor genes. Loss of heterozygosity at chromosome arms 8p, 10q, 13q, and 17p...

Results Of Gene Expression Analysis Of Prostate Cancer

The subset of genes expressed in normal and neoplastic prostate tissue has been estimated based on theoretical and practical considerations. These studies are beginning to define the prostate cancer transcriptome and a possible role for some genes in critical processes. The Cancer Genome Anatomy Project (CGAP) of the National Cancer Institute was designed to identify genes responsible for cancer by sequencing of cDNA clones representing RNA from normal, precancerous, and malignant cells (http...

Other Applications Of Microarrays In Bladder Cancer Research

In addition to expression profiling studies, specific oligonucleotide microarrays have been applied to the study of DNA variation in clinical material. The short length of oligonucleotide targets gives them the ability to discriminate between multiple probes that differ in sequence at a single base. Because of this, oligonucleotide microarrays have been developed to identify simple polymorphisms and allelic variations in DNA (10). The primary applications of these types of microarrays have been...

Data Management And Informatics

The BPC staffs includes three informatics-related employees (computer engineer, programmer, and database liaison). The computer engineer is on staff during system design and redesign and is only cost-effective as a temporary position. The programmer is needed full-time, because systems are always being amended to meet the changing needs of the groups. The database liaison works with the staff in assuring that the systems are meeting the needs of the users (defining them for the programmer) and...

Using Oligonucleotide Microarrays

Sample Preparation Avoiding the Pitfalls A major challenge in using either cDNA or oligonucleotide arrays for tumor profiling is navigating the many pitfalls associated with tissue selection and preparation. Low sample quality probably underlies many apparent inconsistencies across micro-array studies and has seriously marred the clinical relevance of many reports. One problem is that messenger RNA is a very labile molecule, which is susceptible to degradation by the RNases abundantly present...

Sage Uses In Human Genome Mining And Annotation

As previously mentioned, SAGE data is perpetual, and available databases become constantly updated in parallel with our constant improvement in understanding the complete human genome. A recent development of value in helping to better mine the human genome was the report of a modification of the SAGE technique that allows one to obtain longer SAGE tags. This will lead to a better and unique gene identification of the 3' ends of genes and, in turn, facilitates the isolation of novel genes. This...

Iiikiiiiiiiiibiiiimh Mil IiiI III11 mil em Bill

Gene expression clusters and histologic differentiation within lung adenocarcinoma subclasses. Genes expressed at high levels in specific subsets of adenocarcinomas. (A) Colon metastases. (B) Proliferation-related gene expression (C1). (C) NE gene expression (C2). (D) ODC and surfactant gene expression (C3) and C2. (E) Type II pneumocyte gene expression (C4), C3, and normal lung. (F) Histopathological degree of differentiation (red, poor yellow, moderate green, well white, not available...

Molecular Genetics Of Colon Cancer

Colorectal cancer is a well-defined clinical model for studying the molecular events of tumor development and progression. There is a linear progression, during which the neoplasm develops from hyperplastic epithelium in aberrant crypt foci through adenoma to carcinoma and metastasis (28). This sequence reflects the accumulation of specific genetic alterations. It is thought that five to seven genes must be altered sequentially in order for cancer to develop (10). Two separate sequences of...

And Epidemiology Of Prostate Cancer

The vast majority of malignant tumors of the prostate are epithelial and termed adenocarcinomas. The prostate normally has several types of epithelial cells. Basal cells are located between the luminal cells and the basement membrane and form a continuous layer in the non-neoplastic gland. This cell layer may also contain a stem cell compartment that differentiates into luminal cells. Neuroendocrine cells are androgen-independent cells dispersed throughout the basal layer and are believed to...

Current State Of Molecular Biology Of Pancreatic Cancer

A brief review of the current understanding of the genetic alterations associated with pancreatic cancer will help set the stage for a more detailed discussion of gene expression in pancreatic cancer. The last decade has seen a dramatic increase in our understanding of the molecular biology of pancreatic cancer, with pancreatic cancer now considered one of the better characterized neoplasms at the genetic level. Recent advances include the identification of the precursor lesions of invasive...

Unsupervised Learning Clustering

In unsupervised learning techniques, the structure in a data set is elucidated without using any a priori assumptions or knowledge as part of exploratory data analysis. The promise of these methods lies in their ability to provide a molecular grouping or taxonomy of samples or genes. One of the easiest ways to analyze data in this context is by using a clustering algorithm (11-13). Objects of interest, usually genes or samples, are Fig. 2. General methodology for clustering gene expression...

Using Human Bladder Cancer Specimens

Gene expression patterns may vary sufficiently to complicate the task of sample classification based upon expression profiles. A significant challenge lies in choosing the best groups of genes with which to identify the biologically related tumor subclasses. Certain groups or clusters of genes vary consistently in tumor samples, and these genes can frustrate attempts at subclassification (36,37). Tumor classifications based upon these types of dominant gene clusters are unlikely to identify...

Erbb3

Expression Patterns Related to ER Status Tamoxifen is a frequently prescribed drug for treatment and prevention of breast cancer (7,11,90). ER+ tumors may initially respond to tamoxifen, but the development of tamoxifen resistance is an important clinical problem. A number of groups have compared microarray data of breast carcinomas based on ER status. Hilsenbeck et al. (91) compared gene expression arrays of estrogen-stimulated, tamoxifen-sensitive, and resistant MCF-7 cells grown in a nude...

Clinical Manifestations Of Colorectal Cancer

A major goal of global expression analysis is to provide information that supports an enriched system of classification, either alone or in conjunction with clinical and genetic data. To place this effort in perspective, we sketch the clinical behavior of colon cancer and outline the major clinical-pathological classification systems. Adenocarcinoma arises in the epithelial cells of the colon. The tumor consists of a mass of abnormal glands (hence the name, adenocarcinoma) that invades and,...

Background

These account for approx 20 of all primary tumors of bone, with the majority arising in the second decade, the period of maximal skeletal growth (1). While most of these neoplasms arise sporadically, familial cases have been reported, and there is an increased incidence of osteogenic sarcoma in patients with Li-Fraumeni, Bloom, or Rothmund-Thomson Syndromes, and in patients diagnosed with retinoblastoma (211). There is also an increased incidence of osteosarcoma in patients who have undergone...

Multiclass Classification Classifying Multiple Tumor Types

Multiclass classification problems are inherently more difficult than pairwise comparisons. In this section, we review our efforts to perform multiclass tumor classification 49,50 . We explored the general feasibility of molecular cancer diagnosis of common human tumors solely on the basis of tumor gene expression profiles. We first created a gene expression database containing the expression profiles of 218 tumor samples representing 14 common human cancer classes and devised a multiclass...