title: DecreasedBECN1mRNA Expression in Human Breast Cancer is Associated with Estrogen Receptor-Negative Subtypes and Poor Prognosis.
abstract: BothBRCA1andBeclin 1(BECN1) are tumor suppressor genes, which are in close proximity on the human chromosome 17q21 breast cancer tumor susceptibility locus and are often concurrently deleted. However, their importance in sporadic human breast cancer is not known. To interrogate the effects ofBECN1andBRCA1in breast cancer, we studied their mRNA expression patterns in breast cancer patients from two large datasets: The Cancer Genome Atlas (TCGA) (n=1067) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n=1992). In both datasets, low expression ofBECN1was more common in HER2-enriched and basal-like (mostly triple-negative) breast cancers compared to luminal A/B intrinsic tumor subtypes, and was also strongly associated withTP53mutations and advanced tumor grade. In contrast, there was no significant association between lowBRCA1expression and HER2-enriched or basal-like subtypes,TP53mutations or tumor grade. In addition, low expression ofBECN1(but not lowBRCA1) was associated with poor prognosis, andBECN1(but notBRCA1) expression was an independent predictor of survival. These findings suggest that decreased mRNA expression of the autophagy geneBECN1may contribute to the pathogenesis and progression of HER2-enriched, basal-like, andTP53mutant breast cancers.
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.affiliation: Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390 ; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Salwa
authors.initials: S
authors.lastname: Sebti
authors.affiliation: Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390 ; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Rossella
authors.initials: R
authors.lastname: Titone
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Laboratory of Molecular Pathology and Nanobioimaging, Department of Health Sciences, Università del Piemonte Orientale "A Avogrado", Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Isidoro
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 ; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Theodora S
authors.initials: TS
authors.lastname: Ross
authors.affiliation: Department of Pathology and Cell Biology, Columbia University College of Physicians & Surgeons, New York, New York 10032.
authors.forename: Hanina
authors.initials: H
authors.lastname: Hibshoosh
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Xiao
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Milton
authors.initials: M
authors.lastname: Packer
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390 ; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390 ; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 ; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390 ; Howard Hughes Medical Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Beth
authors.initials: B
authors.lastname: Levine
keywords: BECN1; BRCA1; autophagy; breast cancer
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