Restriction fragment length polymorphism studies show consistent loss of chromosome 3p alleles in small cell lung cancer patients' tumors.

Abstract

Previous karyotypic analysis of human small cell lung cancer cell lines has demonstrated a consistent deletion of a portion of the short arm of chromosome 3(pl4-23). DNA prepared from tumors and normal tissues obtained from 24 small cell lung cancer and two extrapulmonary small cell cancer patients was hybridized to four probes that detect restriction fragment length polymorphisms within chromosome region 3p14-21. Of the 25 patients who were heterozygous for at least one marker in this region in the DNA from normal tissue, 23 (92%) showed an unequivocal loss of heterozygosity in the DNA from their tumor tissue. From these studies we conclude that loss of alleles from the short arm of chromosome 3 is a consistent finding in unselected small cell lung cancer patients' tumor DNA.

Differential screening of a human chromosome 3 library identifies hepatocyte growth factor-like/macrophage-stimulating protein and its receptor in injured lung. Possible implications for neuroendocrine cell survival.

“…The MSP and RON genes both map to human chromosome 3p21.3, which coincides with the shortest region of deletion described in SCLC, according to both loss of heterozygosity (5) and homozygous deletion analyses (39)(40)(41). Although we did not observe differences between primary lung tumors and adjacent non-neoplastic lung on genomic Southern blots probed with MSP clone 1697, this type of analysis would not detect point mutations or alterations in other regions of the MSP gene.…”

Differential DNA sequence deletions from chromosomes 3, 11, 13, and 17 in squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma of the human lung.

“…For chromosome 17, the region D17S1 was heterozygous in the constitutive DNA of 11 patients; reduction to homozygosity was seen in only 2 tumors. Thirteen of the adenocarcinoma patients were heterozygous for loci on chromosome 3; among these, 7 of the tumors showed loss of heterozygosity. Loss of heterozygosity was most frequent at the RAF] locus (3 of 5) as compared with the D3S2 (4 of 9) and the DNF15S2 (3 of 8) loci.…”

Oncogenes and tumor-suppressor genes.

“…Interestingly, in squamous cell carcinoma, consistent LOH was found at 17pi3 using the D17S1 probe, while consistent LOH at this locus in adenocarcinomas and large cell carcinomas was not detected. Frequent LOH at this locus has also been associated with colorectal (57-59) and small cell carcinoma of the lung (53,55,60,61).…”

“…LOH on chromosome 3 has been reported in small cell carcinomas (53)(54)(55)(60)(61)(62). It has been speculated that this region contains a putative tumor-suppressor gene for small cell carcinomas of the lung (53).…”