Genomic Profiling of Adenoid Cystic Carcinomas of the Breast.
Maria-Angeles Lopez-Garcia, Daniel Wetterskog, Maryou B Lambros, Felipe C Geyer, Radost Vatcheva, Zoran Gatalica, Britta Weigelt, Jorge S Reis-Filho. Institute of Cancer Research, London, United Kingdom; Hospital Universitario Virgen del Rocio, Seville, Spain; Creighton University Medical Center, Omaha; CRUK London Research Institute, United Kingdom
Background: Adenoid cystic carcinoma (AdCC) of the breast is a rare type of breast cancer, of histological low grade, and of triple negative and basal-like phenotype. Genome-wide genetic aberrations in AdCCs have so far only been investigated in AdCCs of the salivary gland but not AdCCs of the breast. The only genomic aberration reported for breast AdCCs is the chromosomal translocation t(6;9) leading, primarily, to the fusion of the oncogene MYB with the transcription factor NFIB. The aims of this study were to determine whether breast AdCCs are entities distinct from histological grade- matched invasive ductal carcinomas (IDC-NSTs) and of basal-like IDC-NSTs.
Design: Seventeen AdCCs of the breast were microdissected and subjected to genetic analysis with high-resolution microarray-based comparative genomic hybridisation (aCGH). aCGH profiles for breast AdCCs were compared to those of histological grade- matched IDC-NSTs and basal-like IDC-NSTs. Unsupervised and supervised aCGH analysis methods were employed.
Results: aCGH analysis revealed that breast AdCCs display 'simplex' genomic profiles, lacking amplifications and having common regions (>40%) of gains on 16p13.3, 17q, 1p36, 4p16, 11p15, 12p13.3, and loss on 6q23.3-q27. AdCCs significantly less frequently harboured the copy number aberrations found in the grade-matched IDC-NSTs, including gains of 1q and 16p or losses of 8p, 11q, 16q and 22q. Moreover, AdCCs of the breast significantly differed from basal like IDC-NSTs at the genomic level, given that they less frequently harboured gains of 6p, 8q and 10p and losses of 5q, 12q, and 15q. In fact, significant differences between AdCCs and grade-matched and basal-like IDC-NSTs affected 22% and 54% of the genome, respectively.
Conclusions: AdCCs of the breast showed significantly lower levels of genetic instability and copy number aberrations than grade-matched and basal-like IDC-NSTs. Based on the patterns of copy number changes, breast AdCCs represent a distinct entity from both grade-matched and basal-like IDC-NSTs. The low level of genetic instability indicate that other genetic aberrations such as the MYB-NFIB fusion transcript may be responsible for the pathogenesis in the majority of the AdCCs of the breast.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 16, Tuesday Afternoon