Frequent loss of heterozygosity on chromosome 5 in non-small cell lung carcinoma

Abstract

Aims: Loss of heterozygosity (LOH) at specific chromosomal regions strongly suggests the existence of tumour suppressor genes at the relevant segment. Frequent LOH on chromosome 5q has been reported in a wide variety of human tumours, including those of the lung. The aim of this study was to screen for LOH and to clarify the location of putative tumour suppressor genes on chromosome 5 implicated in the genesis and/or development of non-small cell lung carcinoma.

Methods: Thirty three patients with advanced non-small cell lung carcinoma were screened for LOH with a panel of 21 microsatellite DNA markers spanning the entire chromosome 5, using semi-automated fluorochrome based methodology.

Results: Twenty of the non-small cell lung carcinoma samples displayed LOH for one or more informative locus. LOH involving only 5q was found in 10 of 14 of the informative samples. Deletions involving 5p only were not present in the samples under study. There was no evidence of microsatellite instability in any of the analysed loci. These results indicate the presence of five distinct segments displaying high frequencies of deletion on chromosome 5, namely: 5q11.2-q12.2, 5q15 (D5S644 locus), 5q22.3-q23.1, 5q31.1, and 5q35.3. Eight of 14 samples had simultaneous interstitial deletions in at least two different regions. Moreover, concomitant deletion of three and four distinct regions was displayed in three of 14 and two of 14, respectively, of the informative samples.

Conclusion: Allelic deletion on chromosome 5 is a frequent event in patients with non-small cell lung carcinoma. These results suggest the involvement of these five regions, either independently or simultaneously, in both lung squamous cell carcinoma and lung adenocarcinoma.

Figure 1

Retention and loss of heterozygosity (LOH). (A) Example of a sample showing retention of heterozygosity; the normal and tumour DNA profiles are identical. (B) Example of a sample displaying LOH; an arrow indicates a reduction in one of the tumour alleles when compared with the matched constitutional DNA.

Figure 2

Allelotyping results in non-small cell lung carcinoma. AC, adenocarcinoma; SCC, squamous cell carcinoma; black rectangles, loss of heterozygosity; white rectangles, retention of heterozygosity; grey rectangles, uninformative.