Characterization of a candidate tumor suppressor gene on chromosome 3
- Univ. of Texas Health Science Center, San Antonio, TX (United States); and others
Small cell lung cancer (SCLC) tumors frequently display deletions on the short arm of chromosome 3 suggesting the existence of a tumor suppressor gene(s) within that region. The hybrid, HA(3)BB9F, contains a small fragment of human chromosome 3(p22-p21) in mouse A9 cells and is suppressed for tumor formation. Further we have identified a SCLC cell line, NCI H740, that bears a homozygous deletion involving the loss of 6 markers that map to the region 3p21.3-p21.2 and all but one are located within the 3p fragment exhibiting properties of tumor suppression in the HA(3)BB9F hybrid. A homozygous deletion overlapping found in NCI H740 has been identified in a Dutch SCLC cell line. To define the extent of the deletion in NCI H740, we have constructed a YAC and P1 contig spanning 2 Mb. The order of markers within the contig is as follows: -D8-(1,2)-D3S1235-ALU5-ALU342-ALU6-DDI-(3,4)-GNAI2. An SstII fragment corresponding to a CpG island from P1 170 was used to isolate 5 overlapping cDNA clones. These clones detect both DNA rearrangements and altered expression patterns in a proportion of SCLC cell lines. SSCP analysis is being used to identify mutations in those SCLC cell lines which express the gene as assessed by both Northern and RT-PCR analyses. As functional evidence is final proof for tumor suppressor activity, the P1 clones and cDNA have been transfected into a mouse fibrosarcoma (A9) and a human SCLC cell line. A9 transfectants containing the P1 170 clone exhibit both altered morphology and a high frequency of apoptosis when compared to the non-transfected A9 cells. Stable transfectants will be injected into nude mice to assess the ability of the P1 clones to suppress tumorigenesis in vivo.
- OSTI ID:
- 133333
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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