Genomics

Paper: "Multiple loci identified in a genome-wide association study of prostate cancer Thomas G, Jacobs KB, Yeager M, Kraft P, Wacholde

"We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin-nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial prospective study, by testing 26,958 SNPs in four independent studies (total of 3,941 cases and 3,964 controls). In the combined joint analysis, we confirmed three previously reported loci [two independent SNPs at 8q24 and one in HNF1B (formerly known as TCF2 on 17q); P < 10(-10)].

Paper: The SRD5A2 V89L polymorphism is associated with severity of disease in men with early onset prostate cancer.

"BACKGROUND: Emerging evidence indicates that testosterone (T), and not dihydrotestosterone (DHT), is the most relevant androgen that promotes carcinogenesis in the prostate. Steroid 5-alpha reductase type II (SRD5A2) catalyzes the irreversible conversion of T to DHT in male reproductive organs. Because the SRD5A2 gene is highly polymorphic at codon 89, two SRD5A2 isoforms are expressed that differ in K(m) and V(max) values. The more common and rapid catalytic isoform contains a valine residue at position 89; the slower-catalytic variant contains leucine at this position.

Paper: Effect of genetic variability within 8q24 on aggressiveness patterns at diagnosis and familial status of prostate cancer.

"PURPOSE: Recently, two independent loci located at 8q24 that contribute to prostate cancer risk in men of European origin were identified. EXPERIMENTAL DESIGN: Using Bayesian probability network and logistic regression model, we searched for associations between 34 single-nucleotide polymorphisms (SNP) located at 8q24 and the aggressiveness patterns of prostate adenocarcinoma or familial history of cancers in 823 White Caucasian French men.

Paper: 3p22.1 and 10q22.3 deletions detected by fluorescence in situ hybridization (FISH): a potential new tool for early detection of

"BACKGROUND: Our objective was to study the feasibility of detecting chromosomal deletions at 3p22.1 and 10q22.3 by fluorescent in situ hybridization (FISH) and to examine their distribution in different areas of the airway in patients with non-small cell lung cancer. METHODS: Brush biopsies from the mainstem bronchus on the normal side contralateral to the tumor (NBB) and mainstem bronchus on the tumor side (TBB) were obtained from 122 patients who underwent surgical resection.

Paper: Highly sensitive detection of early-stage pancreatic cancer by multimodal near-infrared molecular imaging in living mice.

"Pancreatic cancer is a serious disease with poor patient outcome, often as a consequence of late diagnosis in advanced stages. This is in large part due to the lack of diagnostic tools for early detection. To address this deficiency, we have investigated novel molecular near-infrared fluorescent (NIRF) in vivo imaging techniques in clinically relevant mouse models of pancreatic cancer. Genome wide gene expression profiling was used to identify cathepsin cystein proteases and matrix metalloproteinases (MMP) as targets for NIRF imaging.

Paper: Molecular profiling in the age of cancer genomics.

"In this new era of cancer genomics, large-scale queries of whole genomic characteristics are now possible not only for research and biological understanding, but also for molecular profiling in the context of patient management and care. Here, we will examine genomic, transcriptomic and proteomic methods of characterizing tumors that may play a role in early diagnosis, classification, prognosis, therapeutic guidance and recurrence surveillance during the entire progression of the disease and treatment cycle.

Paper: "Polygenes, risk prediction, and targeted prevention of breast cancer."

"BACKGROUND: New developments in the search for susceptibility alleles in complex disorders provide support for the possibility of a polygenic approach to the prevention and treatment of common diseases. METHODS: We examined the implications, both for individualized disease prevention and for public health policy, of findings concerning the risk of breast cancer that are based on common genetic variation. RESULTS: Our analysis suggests that the risk profile generated by the known, common, moderate-risk alleles does not provide sufficient discrimination to warrant individualized prevention.

Paper: High-Fidelity DNA Polymerase Enhances the Sensitivity of a Peptide Nucleic Acid Clamp PCR Assay for K-ras Mutations.

"Sensitive detection of tumor-specific point mutations is of interest in both the early detection of cancer and the monitoring of treatment at a molecular level. Recently, peptide nucleic acid (PNA) clamp real-time PCR has provided a time-sparing and sensitive method for the detection of mutations in the presence of a large excess of wild-type DNA. We present the first report that the sensitivity of PNA clamp PCR is limited by the low fidelity of TaqDNA polymerase.

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