[Genes involved in breast cancers]
Toshikazu Ushijima1, Masanobu Abe, Takao Maekita
1Carcinogenesis Division, National Cancer Center Research Institute.
Nihon Rinsho. Japanese Journal of Clinical Medicine
|March 15, 2006
Summary
Targeted cancer therapies rely on specific molecular abnormalities. Trastuzumab targets ERBB2 amplification in invasive ductal carcinomas, while BRCA1/2 mutations and p53 alterations are key in breast cancer development and progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Context:
- Specific molecular abnormalities in cancers serve as critical therapeutic targets.
- Trastuzumab exemplifies successful targeted therapy, particularly for ERBB2-amplified invasive ductal carcinomas.
- ERBB2 amplification (15-30%) and c-MYC amplification (13-19%) are significant in breast cancer, linked to poor prognosis and oncogene activation.
Purpose:
- To highlight key molecular abnormalities in breast cancer.
- To discuss the role of ERBB2, c-MYC, BRCA1/2, and p53 in breast cancer pathogenesis.
- To underscore the importance of molecular profiling for identifying diagnostic and therapeutic targets.
Summary:
- ERBB2 amplification is found in 15-30% of invasive ductal carcinomas, correlating with poor prognosis.
- Germline BRCA1/2 mutations are linked to familial breast cancers; somatic mutations are rare in sporadic cases, but inactivation via promoter methylation is frequent.
- p53 mutations occur in 20-25% of sporadic breast cancers, with pathway inactivation being more common.
Impact:
- Identifies ERBB2 amplification as a key target for breast cancer therapeutics.
- Reveals the distinct roles of germline vs. somatic mutations and methylation in BRCA1/2 inactivation.
- Emphasizes the prevalence of p53 pathway alterations in sporadic breast cancers.
- Suggests that continued molecular analysis will uncover novel diagnostic and therapeutic strategies for cancer.
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