SIGNIFICANCE OF THE LOSS OF HETEROZYGOSIT Y ON THE LONG ARM OF CHROMOSOME-5 (5Q21) IN NONSMALL CELL LUNG-CANCER

BACKGROUND: LOSS Of heterozygosity (LOH) at 5q21, where the APC/MCC ge nes reside, is one of the genetic alterations that caracterizes lung c ancer. The aim of this study was to analyse LOH frequency on chromosom e 5q21 in patients with non-small cell lung cancer and its relationshi p with TNM staging and histological subtypes. PATIENTS AND METHODS: Tu mor and corresponding normal DNA were isolated from 60 patients with n on-small cell lung cancer and a subsequent polymerase chain reaction ( PCR) with microsatellite markers within the APC/MCC region was perform ed. The PCR products were resolved by electrophoresis. The comparison between the normal and tumor DNA patterns allowed us to detect the sam ples harboring LOH. RESULTS: LOH at 5q21 was detected in 20% of the pa tients. LOH at 5q21 was found in 16% of stage I patients, 8% in stage II patients and 40% in stage IIIA patients. A trend towards worse surv ival was detected in stage IIIA patients with LOH at 5q21 (9 months me dian time survival) in comparison with patients without LOH (21 months ), although the difference was not statistically significant (p=0.11). No significant differences in LOH were observed among histological ty pes. In addition, we found no correlation between LOH and higher frequ ency of mutations rate affecting K-ras and p53 genes. CONCLUSIONS: LOH at 5q21 is a frequent genetic alteration in non-small cell lung cance r and correlates with locally advanced disease (stage IIIA). Our resul ts suggest that LOH at the 5q21 region could be a prognostic factor in non-small cell lung cancer.