Denaturing high-performance liquid chromatography for mutation detection and genotyping.

Denaturing high-performance liquid chromatography (DHPLC) is an accurate and efficient screening technique used for detecting DNA sequence changes by heteroduplex analysis. It can also be used for genotyping of single nucleotide polymorphisms (SNPs). The high sensitivity of DHPLC has made this technique one of the most reliable approaches to mutation analysis and, therefore, used in various areas of genetics, both in the research and clinical arena.

Pharmacogenomic and pharmacokinetic determinants of erlotinib toxicity.

Purpose: To assess the pharmacogenomic and pharmacokinetic determinants of skin rash and diarrhea, the two primary dose-limiting toxicities of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib.

Patients And Methods: A prospective clinical study of 80 patients with non-small-cell lung cancer, head and neck cancer, and ovarian cancer was performed. Detailed pharmacokinetics and toxicity of erlotinib were assessed.

Relationship of EGFR mutations, expression, amplification, and polymorphisms to epidermal growth factor receptor inhibitors in the NCI60 cell lines.

Purpose: The mechanism of sensitivity and resistance to epidermal growth factor receptor (EGFR) inhibitors is incompletely understood, particularly in cancers other than non-small-cell lung cancer (NSCLC). To understand the variable response to this class of drugs, we used the NCI60 cancer cell lines. We aimed to determine if there are interactions between EGFR expression, mutations, polymorphisms, and gene amplification, and whether these factors are associated with variability in response to EGFR inhibitors.

Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 and breast cancer risk in Africans.

The UDP-glucuronosylatransferase 1A1 (UGT1A1) gene is involved in the metabolism of estrogen and detoxification of potential carcinogens. The number of TA repeats in the promoter region of UGT1A1 has been linked to breast cancer risk, but results varied by race. We performed a comprehensive assessment of genetic polymorphisms in the UGT1A1 gene, and examined these polymorphisms and TA repeats in relation to breast cancer risk in a case-control study in Nigeria.

Study of the genetic determinants of UGT1A1 inducibility by phenobarbital in cultured human hepatocytes.

UGT1A1 is induced by phenobarbital. We investigated whether three common UGT1A1 variants are associated with the variability in UGT1A1 inducibility. Human hepatocytes were incubated with 2 mM phenobarbital for 2 and 6 days followed by 5 microM SN-38 (1 h), a UGT1A1 probe.

Denaturing high-performance liquid chromatography for mutation detection and genotyping.

Denaturing high-performance liquid chromatography (DHPLC) is an accurate and efficient screening technique used for detecting deoxyribonucleic acid sequence changes by heteroduplex analysis. It can also be used for genotyping of single-nucleotide polymorphisms. The high-sensitivity of DHPLC has made this technique one of the most reliable approaches to mutation analysis and is used in various areas of genetics, both in the research and clinical arena.