Loss of heterozygosity at 7q31 in breast cancer: results from an International Collaborative Study Group. The Breast Cancer Somatic Genetics Consortium.

Loss of heterozygosity (LOH) at 7q31 has been claimed to occur in over 80% of all breast cancers and to be of prognostic significance. This would make this genetic alteration the most common event observed in breast cancer to date. Others, however, have been unable to confirm this high incidence. In this multicenter study, we have complied LOH scorings for three polymorphic markers for 7q31-q32 in 683 breast tumors. Although some significant differences between centers existed, no center reported more than 40% LOH, and the average rate was 19%. Disease-free and overall survival of the patients whose tumors carried LOH at 7q31 did not differ significantly from those patients whose tumors showed retention of heterozygosity at 7q31. In a double-blind scoring of a subset of the raw data, an average discordant rate of LOH scoring of 12% was observed. While startling in itself, this was unable to explain the variation among centers, nor the difference with the initially reported high rate of LOH. We conclude that LOH at 7q31 is not important as a genetic alteration in breast cancer as originally suggested, nor a strong determinant of disease outcome.

Degradation of amyloid-related serum protein SAA by a component present in rabbit and human serum.

After incubation of protein SAA-containing rabbit serum at 37 degrees C overnight, the strength of the precipitation reaction against antiserum to SAA was decreased. This was at east partly due to enzymatic degradation of protein SAA. The enzymatic activity was not strongly associated with the SAA-high-density lipoprotein (HDL) complex, since it sedimented in the preparative ultracentrifuge at a density at which the SAA-HDL complex floats. The degrading component was obtained in concentrated form from rabbit and human sera by adsorption to Sepharose 4B. Degradation of human SAA by the human serum component was inhibited with disopropyl fluorophosphate, an inhibitor of serine proteases.