A HOMOZYGOUS DELETION ON CHROMOSOME-3 IN A SMALL-CELL LUNG-CANCER CELL-LINE CORRELATES WITH A REGION OF TUMOR-SUPPRESSOR ACTIVITY

Small cell lung cancer (SCLC) tumors frequently display deletions on t he short arm of chromosome 3 suggesting the existence of a 'tumor supp ressor' gene within that region whose functional inactivation may be i nvolved in tumorigenesis. Recently, a hybrid, HA(3)BB9F, was identifie d that contains a small fragment of human chromosome 3 of approximatel y 2 Mb on a mouse (A9) background (Killary et. al., 1992). This hybrid was utilized to define a functional tumor suppressor gene within 3p22 -p21 which could suppress the tumorigenic properties of the mouse fibr osarcoma cell line. The existence of a tumor suppressor gene in the re gion 3p22-p21 is supported by the present report which describes the a ssessment of 89 SCLC and 32 non-SCLC lung cancer tumors and cell lines for the existence of a homozygous deletion(s) at 43 loci on the short arm of chromosome 3. One of the SCLC cell lines was found to harbor a homozygous deletion involving the loss of five markers on chromosome 3p. All five of the markers map to the region 3p21.3-p21.2 and four of the five markers are located within the chromosome 3 fragment exhibit ing properties of tumor suppression in the HA(3)BB9F hybrid. The other tumors analysed all retained at least one copy of each of the markers assessed.