MYB-NFIB Gene Fusion: A Characteristic Feature of Adenoid Cystic Carcinoma of the Breast.
Daniel Wetterskog, Maria-Angeles Lopez-Garcia, Maryou B Lambros, Felipe C Geyer, Cecilia Cabral, Radost Vatcheva, Kay Savage, Britta Weigelt, Jorge S Reis-Filho. Institute of Cancer Research, London, United Kingdom; Hospital Universitario Virgen del Rocio, Seville, Spain; Cancer Research UK, London Research Institute, United Kingdom
Background: Adenoid cystic carcinoma (AdCC) of the breast is a rare form of triple negative (i.e. oestrogen receptor, progesterone receptor and HER2 negative) breast cancer which is reported to have a favourable clinical outcome. A recent study has demonstrated in a small number of breast AdCCs that these tumours harbour a chromosomal translocation t(6;9) (q22–23;p23–24) leading to the formation of a fusion transcript involving the MYB and NFIB genes. The MYB-NFIB fusion gene is reported to lead to overexpression of MYB and to have oncogenic properties. In this study, we sought to investigate the prevalence of the t(6;9) (q22–23;p23–24) and the MYB-NFIB fusion gene in a large series of breast AdCCs.
Design: Sixteen cases diagnosed as AdCCs of the breast were reviewed by 3 pathologist with an interest in breast cancer. The presence of the t(6;9) (q22–23;p23–24) translocation was investigated by fluorescence in situ hybridisation (FISH) with in-house produced split-apart and fusion probes. Expression of the fusion gene transcript was analysed by reverse transcription polymerase chain reaction (RT-PCR) and direct-sequencing of RNA obtained after tumour microdissection.
Results: The t(6;9) (q22–23;p23–24) translocation was detected in 13 of 16 of the diagnosed AdCCs of the breast using FISH. RT-PCR confirmed the presence of the fusion gene transcript and the breakpoint was separately confirmed by direct sequencing of the products. Histological review of two of the cases lacking the fusion gene revealed them to be adenomyoepitheliomas with AdCC-like features. One bona fide AdCC of the breast lacked the t(6;9) (q22–23;p23–24) translocation and the MYB-NFIB fusion transcript.
Conclusions: The vast majority of breast AdCCs do harbour the MYB-NFIB fusion gene. Our study provides direct evidence, however, that a subset of AdCCs of the breast does not harbour the t(6;9) (q22–23;p23–24) translocation and is potentially driven by other oncogenic events.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 18, Tuesday Afternoon