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. 2011 Mar;28(3):319-26.
doi: 10.1007/s10585-011-9375-y. Epub 2011 Jan 21.

Alterations of the retinoblastoma gene in metastatic breast cancer

Elisabet Ognedal Berge  1 , Stian Knappskog, Johan Richard Lillehaug, Per Eystein Lønning
Affiliations

Alterations of the retinoblastoma gene in metastatic breast cancer

Elisabet Ognedal Berge et al. Clin Exp Metastasis. 2011 Mar.

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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Figures

Fig. 1
Fig. 1
Schematic presentation of RB1 alterations observed in metastatic breast cancer
Fig. 2
Fig. 2
Diagram showing the distribution of RB1 deletions and amplifications seen by us in metastatic breast cancer lesions analyzed in this study (bottom) and primary breast cancer samples (top) in a previous study [15]
See this image and copyright information in PMC

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