Frequent involvement of chromosome 3p alterations in lung carcinogenesis: allelotypes of 215 established cell lines at six chromosome 3p loci.

Abstract

We have determined the allelotypes of 215 established lung cancer cell lines by PCR analysis at six loci on the short arm of chromosome 3 (3p): D3S3 (3p12-p13), D3S30 (3p13), D3S2 (3p14-p21.1), D3S32 (3p21), D3F15S2 (3p21), and THRB (3p24). Eighty-seven small cell lung cancer (SCLC), 93 non-small cell lung cancer (NSCLC), 6 extrapulmonary SCLC, 6 mesothelioma, and 23 normal B lymphocyte (BL) cell lines were analyzed. Low levels of heterozygosity at all six 3p loci were seen in both the SCLC and NSCLC cells. SCLC cell lines exhibited the lowest frequencies of heterozygosity at D3S3 (3%), D3S2 (3%), D3F15S2 (10%), and THRB (6%) when compared with frequencies of 8, 42, 48, and 34% at these same loci in the normal population. The lowest frequencies of heterozygosities among the NSCLC cell lines were seen at D3S3 (5%), DF15S2 (17%), and THRB (15%). Adenocarcinoma (Ad) was the only subtype of NSCLC that exhibited any heterozygosity (7%) at D3S3. In addition to D3S3, the lowest frequencies of heterozygosity were seen at D3F15S2 for Ad (9%), D3S2 for large cell carcinomas (8%), and THRB for adenosquamous (0%), bronchioloalveolar (0%), and large cell (8%) carcinomas. In summary, the 3p chromosome region near the D3S3 locus (3p12-p13) appears to be involved in all forms of lung cancer with additional involvement of regions close to the D3S2 (3p14-p21.1), D3F15S2 (3p21), and THRB (3p24) loci.