FREQUENT MICROSATELLITE INSTABILITY IN PRIMARY SMALL-CELL LUNG-CANCER

Alterations in microsatellite sequences characterize hereditary nonpol yposis colorectal cancer. This microsatellite instability is due in so me kindreds to a germline mutation of the mismatch repair gene hMSH2 o n chromosome 2p. Although microsatellite alterations have been reporte d in other hereditary nonpolyposis colorectal cancer-associated tumors including endometrial and gastric cancers, such changes were not dete cted in most other major neoplasms. We found that 15 of 33 (45%) prima ry small cell lung cancers, tumors not found in the hereditary nonpoly posis colorectal cancer syndrome, displayed alterations of microsatell ite loci which consisted of deletions or expansions of (CA)(n) dinucle otide repeats. In 8 of these 15 neoplasms, microsatellite instability was detected in more than 10% of all tested alleles. However, small ce ll lung cancers that revealed instability contained widespread allelic loss and had a uniformly poor prognosis. These results expand conside rably the known spectrum of tumors with microsatellite instability.