Mutational analysis of the macrophage scavenger receptor 1 (MSR1) gene in primary lung cancer.

Abstract

Allelic deletion at chromosome 8p21-25 is an early and frequent event in the carcinogenesis and development of various cancers. To facilitate investigation of alterations of the macrophage scavenger receptor 1 (MSR1), which is located on 8p22, and to determine the role of this gene in human carcinogenesis and tumor progression, we determined intronic primers designed to amplify the coding region. Since frequent deletion of 8p21-23 has been previously reported in lung cancer, we searched for mutations throughout the coding sequence of the MSR1 gene within a panel of genomic DNA samples obtained from 30 primary lung cancers. Our approach, which involved polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct DNA sequencing, revealed nucleotide variants of the MSR1 gene in only one of the 30 cases examined, with this sample displaying both a 6 bp deletion and a thymine-to-cytosine substitution, the latter occurring within intron 7. The 6 bp deletion was located at a DNA microsatellite region and the thymine-to-cytosine substitution seemed to be a polymorphism. These results suggest that the MSR1 gene is not commonly mutated in lung cancer and not important in susceptibility to lung cancer. Further studies may focus on alternative mechanisms through which the MSR1 gene might be inactivated, such as aberrant DNA methylation, and/or pursue analyses of other genes on 8p21-23 for mutational events. Nevertheless, the panel of intronic PCR primer pair sequences presented here will facilitate future studies to determine the full spectrum and frequency of genetic events that may affect expression/activity of the MSR1 gene in human tumors.