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Loss of heterozygosity at 11q22-q23 in breast cancer
S L Carter1, M Negrini, R Baffa
1Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Abstract:
Studies of loss of heterozygosity (LOH) in breast tumor DNA suggest that several tumor suppressor genes participate in the pathogenesis of breast cancer. Although the short arm of chromosome 11 has been implicated in breast cancer development, no previous LOH studies have indicated the involvement of a suppressor gene on 11q in breast carcinoma. To this end, tumor samples and corresponding normal tissue were collected from 62 unselected patients with primary breast cancer, and the extracted DNA was analyzed by polymerase chain reaction using microsatellite markers on chromosome 11. We found that 39% of the tumors (22 of 57 informative cases) revealed allelic loss in the region 11q22-23, and this loss was independent of LOH found to occur on 11p15. Interestingly, more than 90% of the tumors showed concordant loss of alleles at both 11q and 17p. The marker D11S528, showing LOH in 39% of informative cases, had the highest frequency of LOH among the markers that were used. The data presented indicate that the common overlapping region of LOH is between the loci D11S35 and D11S29, suggesting that this area contains a tumor suppressor gene frequently lost in breast cancer.
Insights
This study investigated loss of heterozygosity (LOH) in breast cancer. Researchers identified a frequently lost tumor suppressor gene region on chromosome 11q22-23, crucial for breast cancer development.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Loss of heterozygosity (LOH) in breast tumor DNA suggests tumor suppressor gene involvement in breast cancer pathogenesis.
- The short arm of chromosome 11 (11q) has been implicated in breast cancer, but specific suppressor genes on 11q were not previously identified through LOH studies.
Purpose of the Study:
- To investigate the involvement of a tumor suppressor gene on chromosome 11q in breast carcinoma using LOH analysis.
- To identify specific regions of allelic loss on chromosome 11 in primary breast cancer tissues.
Main Methods:
- DNA was extracted from tumor and normal tissue samples from 62 primary breast cancer patients.
- Polymerase chain reaction (PCR) with microsatellite markers on chromosome 11 was used to analyze LOH.
- Analysis focused on regions 11q22-23 and 11p15, and compared with LOH at 17p.
Main Results:
- 39% of informative breast tumors (22/57) showed allelic loss in the 11q22-23 region, independent of LOH on 11p15.
- Over 90% of tumors exhibited concordant LOH at both 11q and 17p.
- The marker D11S528 showed the highest LOH frequency (39%), and the common overlapping region of LOH was between D11S35 and D11S29.
Conclusions:
- The data suggest a tumor suppressor gene is located in the 11q22-23 region, specifically between D11S35 and D11S29, and is frequently lost in breast cancer.
- The high frequency of concordant LOH at 11q and 17p suggests a potential functional relationship or coordinated loss in breast cancer development.