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Analysis of oncogenes and tumor suppressor genes in human breast cancer
H Yamashita1, S Kobayashi, H Iwase
1Second Department of Surgery, Nagoya City University Medical School.
Abstract:
Oncogenes (c-erbB-2, c-myc, and some genes linked to the 11q13 lesion), tumor suppressor genes (retinoblastoma gene, p53) and an antimetastatic gene (nm23/nucleoside diphosphate kinase) play important roles in breast cancer progression. Amplification of c-erbB-2, c-myc, and int-2, and expression of RB, p53(mutant), and NDP kinase were determined in 77 primary breast cancer specimens. nm23-H1 allelic loss was also studied. c-erbB-2 and c-myc amplification, loss of RB expression, p53(mutant) expression, and nm23-H1 allelic loss were also found in non-invasive carcinoma. int-2 amplification was significantly correlated with lymph node status (P = 0.02) and a significant association was found between p53(mutant) expression and tumor size (P = 0.04). c-erbB-2 amplification was strongly associated with disease-free and overall survival in multivariate analysis (P = 0.002). All of the c-erbB-2 amplified cases and all but one of the int-2 amplified cases in node-positive patients had relapsed within 2 years post resection. The cancer cells may acquire new proliferative pathways sequentially as a result of multiple genetic alterations which enable them to bypass the estrogen-dependent proliferation.
Insights
Key breast cancer genes like c-erbB-2 and p53 influence tumor progression and patient survival. Genetic alterations in oncogenes and tumor suppressor genes are linked to disease advancement and recurrence risk.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer progression involves critical oncogenes (c-erbB-2, c-myc), tumor suppressor genes (retinoblastoma gene, p53), and antimetastatic genes (nm23/nucleoside diphosphate kinase).
- Understanding the roles of these genetic factors is crucial for predicting breast cancer outcomes.
Purpose of the Study:
- To investigate the amplification and expression of key genes involved in breast cancer progression in primary tumor specimens.
- To correlate genetic alterations with clinical parameters such as tumor size, lymph node status, and patient survival.
Main Methods:
- Analysis of gene amplification (c-erbB-2, c-myc, int-2) and gene expression (RB, p53, NDP kinase) in 77 primary breast cancer samples.
- Assessment of nm23-H1 allelic loss.
- Multivariate analysis to determine associations between genetic alterations and clinical outcomes.
Main Results:
- Gene alterations including c-erbB-2 amplification, RB loss, mutant p53 expression, and nm23-H1 allelic loss were observed even in non-invasive cancers.
- int-2 amplification correlated significantly with lymph node status (P=0.02).
- Mutant p53 expression was associated with tumor size (P=0.04), and c-erbB-2 amplification strongly predicted disease-free and overall survival (P=0.002).
Conclusions:
- Genetic alterations in oncogenes and tumor suppressor genes are early events in breast cancer development and progression.
- Specific genetic changes, particularly c-erbB-2 amplification, are significant prognostic markers for breast cancer patients.
- Sequential genetic alterations may drive tumor progression and enable estrogen-independent proliferation, impacting relapse rates.