Pooled analysis of LOH in breast cancer finds many nonreproducible results.

2004 FEB 5 - (NewsRx.com & NewsRx.net) -- Researchers compile a database of loss of heterozygosity (LOH) studies of breast cancer that lays a framework for further investigation.

"Somatic loss of heterozygosity (LOH) has been widely reported in breast cancer as a means of identifying putative tumor-suppressor genes. However, individual studies have rarely spanned more than a single chromosome, and the varying criteria used to declare LOH complicate efforts to formally differentiate regions of consistent versus sporadic (random) loss," scientists in the United States report.

"We report here the compilation of an extensive database from 151 published LOH studies of breast cancer, with summary data from 115,000 tumors and primary allelotypes from 14,300 tumors," wrote B.J. Miller and colleagues, University of North Carolina, Department of Biostatistics.

"Allelic loss was evaluated at 1,168 marker loci, with large variation in the density of informative observations across the genome. Using studies in which primary allelotype information was available, we employed a likelihood-based approach with a formal chromosomal instability and selection model," the researchers wrote.

"The approach seeks direct evidence for preferential loss at each locus compared with nearby loci, accounts for heterogeneity across studies, and enables the direct comparison of candidate regions across the genome. Striking preferential loss was observed (in descending order of ...