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Loss of heterozygosity in a gene coding for a thyroid hormone receptor in lung cancers
Abstract:
The ERBA beta gene codes for a DNA-binding thyroid hormone receptor (THR) and maps to chromosome 3p21-p25, overlapping a 3p deletion characterizing small-cell lung carcinoma (SCLC). A DNA clone detecting an RFLP at the ERBA beta locus has been used to probe a large number of lung tumors. Virtually all SCLC had lost heterozygosity, showing that the 3p deletion in SCLC includes this gene. A substantial but smaller proportion of non-small-cell carcinomas had lost heterozygosity at ERBA beta. Among all non-small-cell tumors some had lost heterozygosity at the proximal locus DNF15S2 (band 3p21) but not at ERBA beta, whereas none were found where the reverse was true. Therefore, the locus which plays a role in non-small-cell tumorigenesis probably lies closer to DNF15S2 than to ERBA beta and is almost certainly not the latter.
Insights
Small-cell lung carcinoma (SCLC) frequently involves a deletion on chromosome 3p that includes the ERBA beta gene. This gene, coding for a thyroid hormone receptor, is often lost in SCLC tumors, suggesting its role in the cancer's development.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- The ERBA beta gene, encoding a DNA-binding thyroid hormone receptor (THR), is located on chromosome 3p21-p25.
- This chromosomal region is frequently deleted in small-cell lung carcinoma (SCLC).
Purpose of the Study:
- To investigate the involvement of the ERBA beta gene in lung tumorigenesis.
- To determine if the ERBA beta gene is part of the 3p deletion commonly observed in SCLC.
Main Methods:
- Utilized a DNA clone detecting a restriction fragment length polymorphism (RFLP) at the ERBA beta locus.
- Analyzed a large cohort of lung tumors, including SCLC and non-small-cell lung carcinomas (NSCLC), for loss of heterozygosity (LOH) at the ERBA beta locus.
- Assessed LOH at the DNF15S2 locus (3p21) in NSCLC to further delineate the critical region.
Main Results:
- Virtually all SCLC samples exhibited LOH at the ERBA beta locus, confirming its inclusion in the 3p deletion characteristic of SCLC.
- A significant proportion of NSCLC also showed LOH at ERBA beta, though less frequently than in SCLC.
- In NSCLC, LOH at the proximal locus DNF15S2 (3p21) was observed without concurrent LOH at ERBA beta, but the reverse was not seen.
Conclusions:
- The ERBA beta gene is frequently implicated in SCLC development due to its location within the commonly deleted 3p region.
- The critical locus involved in non-small-cell lung tumorigenesis is likely located closer to DNF15S2 than to ERBA beta and is probably not ERBA beta itself.