Limits...
Decreased BECN1 mRNA Expression in Human Breast Cancer is Associated with Estrogen Receptor-Negative Subtypes and Poor Prognosis.

Tang H, Sebti S, Titone R, Zhou Y, Isidoro C, Ross TS, Hibshoosh H, Xiao G, Packer M, Xie Y, Levine B - EBioMedicine (2015)

Bottom Line: In both datasets, low expression of BECN1 was 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 with TP53 mutations and advanced tumor grade.In contrast, there was no significant association between low BRCA1 expression and HER2-enriched or basal-like subtypes, TP53 mutations or tumor grade.In addition, low expression of BECN1 (but not low BRCA1) was associated with poor prognosis, and BECN1 (but not BRCA1) expression was an independent predictor of survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390.

ABSTRACT

Both BRCA1 and Beclin 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 of BECN1 and BRCA1 in 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 of BECN1 was 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 with TP53 mutations and advanced tumor grade. In contrast, there was no significant association between low BRCA1 expression and HER2-enriched or basal-like subtypes, TP53 mutations or tumor grade. In addition, low expression of BECN1 (but not low BRCA1) was associated with poor prognosis, and BECN1 (but not BRCA1) expression was an independent predictor of survival. These findings suggest that decreased mRNA expression of the autophagy gene BECN1 may contribute to the pathogenesis and progression of HER2-enriched, basal-like, and TP53 mutant breast cancers.

No MeSH data available.


Related in: MedlinePlus

Boxplot showing the distribution of BECN1 expression and BRCA1 expression in METABRIC according to the copy number status (panels A and B), PAM50 subtypes (panels C and D), TP53 mutation status (panels E and F), tumor grade (panels G and H), and PAM50 subtypes in copy number loss subgroups (panels I and J). The boxes represent the median (black middle line) and the 25th–75th percentiles (lower and upper box borders). Units for gene expression represent log2 intensities of Illumina array values (see Methods).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4376376&req=5

f0010: Boxplot showing the distribution of BECN1 expression and BRCA1 expression in METABRIC according to the copy number status (panels A and B), PAM50 subtypes (panels C and D), TP53 mutation status (panels E and F), tumor grade (panels G and H), and PAM50 subtypes in copy number loss subgroups (panels I and J). The boxes represent the median (black middle line) and the 25th–75th percentiles (lower and upper box borders). Units for gene expression represent log2 intensities of Illumina array values (see Methods).

Mentions: Nonetheless, since the majority of breast cancer cases with BRCA1 or BECN1 copy number alteration contain concurrent deletions of both BRCA1 and BECN1, it is difficult to use copy number alterations as a parameter for distinguishing the effects of these two genes in breast cancer. Genes with a high correlation between their copy number and mRNA expression are more likely to be driver genes and regulate tumorigenesis, since gene expression rather than copy number better defines phenotype (Akavia et al., 2010). Notably, the relationship between copy number loss and mRNA expression was more significant for BECN1 than for BRCA1 in both the TCGA dataset (P = 2.77E− 88 and P = 4.12E− 10, respectively) (Fig. 1A–B) and the METABRIC dataset (P = 6.87E− 31 and P = 5.02E− 8, respectively) (Fig. 2A–B).


Decreased BECN1 mRNA Expression in Human Breast Cancer is Associated with Estrogen Receptor-Negative Subtypes and Poor Prognosis.

Tang H, Sebti S, Titone R, Zhou Y, Isidoro C, Ross TS, Hibshoosh H, Xiao G, Packer M, Xie Y, Levine B - EBioMedicine (2015)

Boxplot showing the distribution of BECN1 expression and BRCA1 expression in METABRIC according to the copy number status (panels A and B), PAM50 subtypes (panels C and D), TP53 mutation status (panels E and F), tumor grade (panels G and H), and PAM50 subtypes in copy number loss subgroups (panels I and J). The boxes represent the median (black middle line) and the 25th–75th percentiles (lower and upper box borders). Units for gene expression represent log2 intensities of Illumina array values (see Methods).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376376&req=5

f0010: Boxplot showing the distribution of BECN1 expression and BRCA1 expression in METABRIC according to the copy number status (panels A and B), PAM50 subtypes (panels C and D), TP53 mutation status (panels E and F), tumor grade (panels G and H), and PAM50 subtypes in copy number loss subgroups (panels I and J). The boxes represent the median (black middle line) and the 25th–75th percentiles (lower and upper box borders). Units for gene expression represent log2 intensities of Illumina array values (see Methods).
Mentions: Nonetheless, since the majority of breast cancer cases with BRCA1 or BECN1 copy number alteration contain concurrent deletions of both BRCA1 and BECN1, it is difficult to use copy number alterations as a parameter for distinguishing the effects of these two genes in breast cancer. Genes with a high correlation between their copy number and mRNA expression are more likely to be driver genes and regulate tumorigenesis, since gene expression rather than copy number better defines phenotype (Akavia et al., 2010). Notably, the relationship between copy number loss and mRNA expression was more significant for BECN1 than for BRCA1 in both the TCGA dataset (P = 2.77E− 88 and P = 4.12E− 10, respectively) (Fig. 1A–B) and the METABRIC dataset (P = 6.87E− 31 and P = 5.02E− 8, respectively) (Fig. 2A–B).

Bottom Line: In both datasets, low expression of BECN1 was 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 with TP53 mutations and advanced tumor grade.In contrast, there was no significant association between low BRCA1 expression and HER2-enriched or basal-like subtypes, TP53 mutations or tumor grade.In addition, low expression of BECN1 (but not low BRCA1) was associated with poor prognosis, and BECN1 (but not BRCA1) expression was an independent predictor of survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390.

ABSTRACT

Both BRCA1 and Beclin 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 of BECN1 and BRCA1 in 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 of BECN1 was 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 with TP53 mutations and advanced tumor grade. In contrast, there was no significant association between low BRCA1 expression and HER2-enriched or basal-like subtypes, TP53 mutations or tumor grade. In addition, low expression of BECN1 (but not low BRCA1) was associated with poor prognosis, and BECN1 (but not BRCA1) expression was an independent predictor of survival. These findings suggest that decreased mRNA expression of the autophagy gene BECN1 may contribute to the pathogenesis and progression of HER2-enriched, basal-like, and TP53 mutant breast cancers.

No MeSH data available.


Related in: MedlinePlus