Many studies have examined DNA copy number changes or gene expression profiling and their association with clinical outcomes in breast cancer. However, until now no study has investigated whether acquired uniparental disomy (aUPD), in which both chromosomes in a pair are derived from the same parent, may have an association with clinical outcome including initiation and recurrence of breast cancer. In this study, we used high-density SNP and expression microarrays data from primary tumors of 313 lymph node-negative breast cancer patients who had not received adjuvant systemic therapy to evaluate the association of aUPD with metastasis-free survival (MFS) and overall survival (OS). In 55.9% (175/313) of the tumors, we defined aUPD, which was most frequent in the regions at chr17q (30.3%) and chr13q (19.4%). In Cox univariate regression analysis including all patients, aUPD at four regions at chr17q, ranging in size from 2.9 to 4.0 Mb, were associated with a poor OS. Only aUPD at one region, region B, on chr17q was associated with a poor MFS. Similarly, aUPD at two regions, A and B, on chr13q, with sizes of 3.5 and 3.1 Mb, were associated with a poor OS, but not with MFS. In ER-subgroup analyses, regions B and D at 17q were associated with poor MFS and OS in ER-negative patients. Various differentially expressed genes within the identified aUPD regions at chr17q were associated with MFS and OS in all patients (PPM1D, C17orf71, and TRIM37) and/or in the ER-negative patients (PPM1D, PPM1E, and SLCA3R1). We thus conclude that aUPD is a frequent event in breast cancer and that aUPD at specific regions in the genome has implications in this disease.

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Keywords Acquired uniparental disomy, Breast cancer, Metastasis-free survival, Overall survival, Prognostic marker
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Journal Breast Cancer Research and Treatment
Tuna, M, Smid, M, Martens, J.W.M, & Foekens, J.A. (2012). Prognostic value of acquired uniparental disomy (aUPD) in primary breast cancer. Breast Cancer Research and Treatment, 132(1), 189–196. doi:10.1007/s10549-011-1579-y