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Oncogenes and human breast cancer
J M Hall1, P J Zuppan, L A Anderson
1School of Public Health, University of California, Berkeley 94720.
American Journal of Human Genetics
|April 1, 1989
Summary
Oncogenes are unlikely to be the primary cause of inherited breast cancer. This study found no genetic linkage between breast cancer susceptibility and nine common oncogenes in affected families.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- The role of oncogenes in breast cancer development remains uncertain.
- Observed alterations in oncogene sequences in breast tumors suggest potential involvement.
- These alterations could represent primary lesions, drivers of progression, or secondary genomic changes.
Purpose of the Study:
- To investigate the genetic linkage between breast cancer susceptibility and nine specific oncogenes.
- To determine if alterations in these oncogenes are associated with inherited predisposition to breast cancer.
Main Methods:
- Analyzed genetic linkage in 12 extended families with 87 affected individuals.
- Calculated Lod scores to assess the probability of close linkage between breast cancer and candidate oncogene sequences.
- Excluded specific chromosomal regions and oncogene alleles from linkage.
Main Results:
- Strong evidence against close linkage between breast cancer susceptibility and HRAS, KRAS2, MYC, MYB, ERBA2, INT2, and RAF1 oncogenes.
- Ruled out linkage to NRAS and excluded specific regions on chromosomes 11p and 3p.
- The MOS oncogene's 5-kb allele, previously implicated, was absent, indicating no association with inherited susceptibility.
Conclusions:
- The study strongly suggests that oncogenes are not the primary sites of alterations leading to inherited breast cancer.
- Alterations in these oncogenes may, however, play a role in tumor progression or metastasis.