LOH of chromosome 12p correlates with Kras2 mutation in non-small cell lung cancer

Abstract

Previous observation has shown that the wild-type Kras2 allele is a suppressor of lung cancer in mice. Here we report that loss of heterozygosity (LOH) of chromosome 12p was detected in approximately 50% of human lung adenocarcinomas and large cell carcinomas, and Kras2 mutations were detected at codon 12 in approximately 40% of adenocarcinomas and large cell carcinomas. Interestingly, all of the lung adenocarcinomas and large cell carcinomas containing a Kras2 mutation exhibited allelic loss of the wild-type Kras2 allele when a correlation between LOH of the region on chromosome 12p and Kras2 mutation was made. These results from human lung cancer tissues provide a strong evidence in support of our previous observation in mouse models that the wild-type Kras2 is a tumor suppressor of lung cancer.

Figure 1

(a) Representative autoradiograph showing LOH in non-small cell lung cancer. Above each autoradiograph, microsatellite marker; under each autoradiograph, patient's identification number; arrowheads, the allele losses; N, normal DNA;T, Tumor DNA. For each sample, the left panel, lung tumor without LOH; the right panel, lung tumor with LOH. (b) Representative example for Kras2 gene codon 12 mutation. On the left, lung tumor without Kras2 mutation; on the right, lung tumor with Kras2 gene 12th codon mutation (GGT→TGT transition)

Figure 2

LOH map of chromosome 12 in non-small cell lung cancers. A total of 12 samples containing a Kras2 mutation exhibited LOH at one or more loci on chromosome 12 Kras2 region. The genetic map of chromosome 12 was derived from NCBI Human Genome Resources. L, large cell carcinoma; A, adenocarcinoma