Is BECN1 a Target Gene of Chromosome 17q21 Alteration in Breast Cancer?

In this issue of EBioMedicine, Tang et al. describes their results obtumour formation due to mammary gland-specific biallelic Palb2 deletained from analysing the expression of BRCA1 and BECN1 in breast cancer patients from two large datasets (TCGA and METABRIC datasets) (Tang et al., 2015). They found reproducible associations in both datasets of BECN1 expression with oestrogen receptor negative cancers (HER2-OE and basal like breast cancers) as well as molecular features related to the subtypes. Intriguingly, no such correlations were found with BRCA1 expression. A similar relationship was also observed in the analysis of BRCA1 deletion cases. In addition, BECN1, but not BRCA1, was shown to be an independent prognostic factor in multivariate analysis. Both BECN1 and BRCA1 are closely located on 17q21, a region frequently deleted in sporadic breast cancers. For many years, BRCA1 has attracted much more attention in breast cancer than BECN1. BRCA1 encodes a multifunctional protein that plays key roles in DNA repair, cell cycle control and transcriptional regulation (Turner et al., 2007). Mutations in BRCA1 are well known to be responsible for the development of familial breast cancer. Although BRCA1 dysfunction has been linked also to basal-like breast cancer, it is important to note that it is mainly based on studies from familial cases with BRCA1 mutation. These cancers shared many phenotypes and gene expression signature associated with basal like breast cancers, suggesting similarities in pathogenic mechanisms (Turner et al., 2007). Although these have been corroborated by some studies in sporadic cancers, controversy still exists among different studies (Rakha et al., 2008). BECN1 is an essential regulator of autophagy. BECN1, with its close proximity with BRCA1, is frequently co-deleted with BRCA1 (Turner et al., 2004). Given that it is a haplo-insufficient tumour-suppressor, its co-deletion with BRCA1 may also contribute to mammary tumorigenesis and cancer characteristics attributable to BRCA1 dysfunction. However, its role in breast cancer remains debatable and may depend on cellular context. Mono-allelic deletion of BECN1 in C67/B6 mice has led to the formation of spontaneous lung and liver cancers as well as lymphoma but only mammary hyperplasia (Qu et al., 2003). However, different results were obtained from other breast cancer models. In ERBB2or PyMT-driven mammary tumorigenesis, there are no effects of monoallelic deletion of BECN1 (Lozy et al., 2014); whereas it delays