A deletion at the short arm of chromosome 3 is common to all major types of lung cancer

Abstract

Abstract Occurrence of short arm deletions of chromosome 3 as a consistent abnormality of small cell lung cancer (SCLC) has been a matter of some dispute. A cytogenetic analysis of cell lines derived from SCLC tumours from different patients delimited the common deletion to 3p21-22. The DNA clone defining D1S1 contains a repetitive element present on chromosome 1, but has been shown to originate from chromosome 3. We localized the clone by in situ hybridization of some of its single copy sequences at 3p21. One subclone, pH3H2, detects a DNA polymorphism with a frequency of heterozygotes close to the maximum of 0.5. The distribution of alleles among lung cancer patients appeared to be similar to that in the general population. By applying pH3H2 in a Southern analysis of both constitutive and tumor DNA from the same lung cancer patients the possible occurrence of 3p21 deletions in SCLC and other types of lung cancer was investigated. All informative cases of SCLC, squamous carcinoma, and adenocarcinoma studied did show loss of an allele at the 3p21 locus DNF15S2 identified by pH3H2. Therefore, some recessive tumor suppressor gene at 3p21 may be involved in the development of lung cancer in general. This agrees with the concept that the different types of lung cancer originate from one common malignantly transformed stem cell population in which different histological characteristics reflect preferentially expressed differentiation pathways.