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Breast cancer is one of the leading causes of cancer mortality in women. Recent advances in gene expression profiling have indicated that breast cancer is a heterogeneous disease and the current prognostication using clinico-pathological features is not sufficient to fully predict therapy response and disease outcome. In this retrospective study, we show that expression levels of BRE, which encodes a member of the BRCA1 DNA damage repair complex, predicted disease-free survival (DFS) in non-familial breast cancer patients. The predictive value of BRE expression depended on whether patients received radiotherapy as a part of their primary treatment. In radiotherapy-treated patients, high BRE expression predicted a favorable DFS (hazard ratio (HR) = 0.47, 95 % confidence interval (CI) = 0.28-0.78, p = 0.004), while in non-treated patients, high BRE expression predicted an adverse prognosis (HR = 2.59, 95 % CI = 1.00-6.75, p = 0.05). Among radiotherapy-treated patients, the prognostic impact of BRE expression was confined to patients with smaller tumors (HR = 0.23, 95 % CI = 0.068-0.75, p = 0.015) and it remained an independent factor after correction for the other prognostic factors age, tumor size, lymph node involvement, and histological grade (HR = 0.50, CI = 0.27-0.90, p = 0.021). In addition, high BRE expression predicted a favorable relapse-free survival in a publicly available dataset of 2,324 breast cancer patients (HR = 0.59, CI = 0.51-0.68, p < 0.001). These data indicate that BRE is an interesting candidate for future functional studies aimed at developing targeted therapies.

Aberrations in protein ubiquitination have recently been identified in the pathogenesis of acute myeloid leukemia (AML). We studied whether expression changes of more than 1600 ubiquitination related genes correlated with clinical outcome in 525 adult AML patients. High expression of one of these genes, BRE, was observed in 3% of the cases and predicted favorable prognosis independently of known prognostic factors (5-year overall survival: 57%). Remarkably, unsupervised expression profiling showed that 86% of high BRE-expressing patients were confined to a previously unrecognized cluster. High BRE expression was mutually exclusive with FLT3 ITD, CEBPA, IDH1, and IDH2 mutations, EVI1 overexpression, and favorable karyotypes. In contrast, high BRE expression co-occurred strongly with FAB M5 morphology and MLL-AF9 fusions. Within the group of MLL-AF9-positive patients, high BRE expression predicted superior survival, while normal BRE expression predicted extremely poor survival (5-year overall survival of 80% vs 0%, respectively, P = .0002). Both the co-occurrence of high BRE expression with MLL-AF9 and its prognostic impact were confirmed in an independent cohort of 436 AML patients. Thus, high BRE expression defines a novel subtype of adult AML characterized by a favorable prognosis. This work contributes to improved risk stratification in AML, especially among MLL-AF9-positive patients.