Alterations of the retinoblastoma gene in metastatic breast cancer |
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Authors: | Elisabet Ognedal Berge Stian Knappskog Johan Richard Lillehaug Per Eystein Lønning |
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Institution: | (1) Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway;(2) Department of Oncology, Haukeland University Hospital, Jonas Lies vei 26, 5021 Bergen, Norway;(3) Department of Molecular Biology, University of Bergen, Bergen, Norway; |
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Abstract: | 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. |
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