Alterations of the retinoblastoma gene in metastatic breast cancer
Autor: | Stian Knappskog, Johan R. Lillehaug, Per Eystein Lønning, Elisabet Ognedal Berge |
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Jazyk: | angličtina |
Předmět: |
Adult
Oncology medicine.medical_specialty Cancer Research Passenger Mitomycin Driver Breast Neoplasms Biology Retinoblastoma Protein Metastasis Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762 [VDP] Breast cancer Germline mutation Surgical oncology Internal medicine Gene duplication medicine Humans Anthracyclines Genes Retinoblastoma Neoplasm Metastasis Retinoblastoma Point mutation General Medicine Middle Aged medicine.disease Metastatic breast cancer eye diseases Gene Expression Regulation Neoplastic Drug Resistance Neoplasm Mutation Female RB1 Chemoresistance Research Paper |
Zdroj: | Clinical & Experimental Metastasis |
ISSN: | 0262-0898 |
DOI: | 10.1007/s10585-011-9375-y |
Popis: | Germline mutations affecting the retinoblastoma gene (RB1) predispose to inherited retinoblastomas but also other malignancies, including breast cancer. While somatic RB1 mutations have been detected in different malignancies, information about the potential role of RB1 mutations in breast cancer is limited. Recently, we discovered RB1 mutations to be associated with resistance to anthracyclines/mitomycin in primary breast cancer. The present work is the first report evaluating RB1 mutation and epigenetic status in metastatic breast cancer. Among 148 breast cancer samples analyzed by MLPA, four samples harbored intragenic deletions/duplications: Thus, exons 1–2 were deleted in two tumors and exons 21–23 in one tumor, while one sample harbored duplication of exons 18–23. The entire RB1 gene was duplicated in two tumors and multiple amplifications were revealed in one sample. Reduced copy number was observed in 17 samples (11.5%). No point mutation or promoter hypermethylation was discovered (n = 38 and 114 tumors analyzed, respectively). Interestingly, among seven tumors expressing lack of response to epirubicin, two samples harbored alterations in RB1, contrasting none out of 16 tumors with stable disease or an objective response (P = 0.08). In summary, the frequency of RB1 alterations in metastatic lesions was not increased when compared to primary breast cancer, indicating that RB1 alterations do not play a major role in metastatic development. While a non-significant association suggesting RB1 alterations to be linked to therapy resistance was observed, our data do not suggest a major role for RB1 alterations explaining acquired drug resistance. publishedVersion |
Databáze: | OpenAIRE |
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