p53 alteration in morphologically normal/benign breast luminal cells in BRCA carriers with or without history of breast cancer
Autor: | David G. Hicks, Kristin A. Skinner, Hengwei Zhang, Xi Wang, Amber A. El-Halaby, Qi Yang, Paul G. Rothberg, Todd S. Laughlin |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Heterozygote Pathology medicine.medical_specialty Heredity DNA Mutational Analysis Population Triple Negative Breast Neoplasms Gene mutation medicine.disease_cause Genomic Instability Germline Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Breast cancer Germline mutation Mutation Rate Biomarkers Tumor medicine Humans Genetic Predisposition to Disease skin and connective tissue diseases education BRCA2 Protein education.field_of_study BRCA1 Protein business.industry medicine.disease Immunohistochemistry Pedigree Cell Transformation Neoplastic Phenotype 030104 developmental biology 030220 oncology & carcinogenesis Mutation Female Triple-Negative Breast Carcinoma Tumor Suppressor Protein p53 Breast carcinoma business Carcinogenesis |
Zdroj: | Human Pathology. 68:22-25 |
ISSN: | 0046-8177 |
Popis: | Germline mutations in BRCA genes have been shown to predispose patients to breast cancer. Studies have suggested that p53 alteration is a necessary step in tumorigenesis in BRCA carriers. Our previous study showed p53 alteration in morphologically normal/benign breast luminal cells in sporadic breast cancer patients, the so-called breast p53 signature. Here, we studied p53 status in 66 BRCA1/2 carriers' breasts: 29 patients with breast carcinoma (2 patients with bilateral breast carcinomas) and 37 without. Seven of the 12 (58%) triple-negative breast carcinomas in BRCA carriers were positive for p53 alteration (immunohistochemical stain and/or sequencing), the same frequency as in sporadic triple-negative breast carcinomas. Focal p53 positivity in adjacent normal/benign luminal cells was identified in 4 of the 7 cases with p53-positive carcinomas but not in breasts with p53-negative carcinomas, indicating that p53 positivity in normal/benign breast luminal cells is not a random event. Furthermore, in BRCA carriers' prophylactic mastectomies, 12 of the 94 (12.77%) breasts had focal p53 positivity in normal/benign luminal cells, with 2 cases in bilateral breasts, significantly higher than in previously studied mammoplasty specimens (0%). Our study suggests that germline BRCA gene mutations could result in genomic instability and an elevated gene mutation rate (such as the p53 gene) in breast luminal cells compared with the general population, predisposing BRCA carriers to develop p53-positive/triple-negative breast carcinomas. |
Databáze: | OpenAIRE |
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