Abstract
It has been proposed that the excess of the familiar risk associated with breast cancer could be explaining by multiple weakly predisposing alleles. Hence there is much interest in the search for low-penetrance genes/variants for breast cancer, which exist with high prevalence in the general population. Maeda and colleagues [1] recently identified the transcriptional repressor FBI1, which they called Pokemon (POK erythroid myeloid ontogenic factor), as a critical factor in oncogenesis. This protein is codified by the ZBTB7 gene ('zing finger and BTB domain containing 7'; GeneID, 51341). Mouse embyronic fibroblasts lacking Zbtb7 were completely refractory to oncogene-mediated cellular transformation. Conversely, FBI1 overexpression led to overt oncogenic transformation both in vitro and in vivo in transgenic mice. FBI1 can specifically repress the transcription of the tumor suppressor gene ARF (600160). Maeda and colleagues [1] found that FBI1 is aberrantly overexpressed in human cancers, and its expression levels predict biologic behavior and clinical outcome. On the other hand, tissue microarray analysis (TMA) in breast carcinomas has revealed high levels of Pokemon expression in a subset of these tumors. In addition, the genomic region where the ZBTB7 gene resides (19p13.3) is a hotspot for chromosomal translocations [2]. ZBTB7 is therefore a good candidate for a breast cancer low-penetrance gene. We aim to determine whether common polymorphisms (frequency ≥ 10%) in the ZBTB7 gene are associated with breast cancer risk in Spanish patients. A set of 22 validated binary SNP polymorphisms were selected from public databases (e.g. HapMap) and private databases (e.g. Celera and RealSNP) according to criteria of coverage (average 1 SNP/1.7 kb). These SNPs cover the flanking regions (10,000 bp), including the promoter region, introns, and coding non-synonymous SNPs. About 550 cases and 550 controls have been genotyped. Genotyping was performed using the MassARRAY SNP genotyping system (Sequenom Inc., San Diego, CA, USA). To our knowledge, this is the first time that the ZBTB7 gene has been analyzed in breast cancer patients. The results will be presented at the time of the congress and will be interpreted in the light of the worldwide population study shown in another presentation from the same authors.
Highlights
Endocrine therapy for breast cancer is a major modality for the treatment of breast cancer, producing response rates between 30% and 40% of unselected patients with the minimum of toxicity
We have shown that overexpression of TGF-β1 in mammary epithelial cells suppresses the development of carcinomas and that expression of a dominant negative type II TGF-β receptor (DNIIR) in mammary epithelial cells under control of the MMTV promoter/enhancer increases the incidence of erbB2 in carcinomas accompanied by Tgfbr2fspKO fibroblasts
We found that the frequency of the IVS10-6T>G is characterized by multiple physiologic abnormalities, including mutation was not increased in breast cancer cases as compared with neurodegeneration, immunologic abnormalities, cancer predisposition, controls
Summary
Endocrine therapy for breast cancer is a major modality for the treatment of breast cancer, producing response rates between 30% and 40% of unselected patients with the minimum of toxicity. Several human genetic diseases are known to be or suspected to be due to defects in DNA repair or cell cycle control Some of these patients are radiation sensitive and/or predisposed for cancer as a cause of mutations in genes involved in these cellular pathways. Microarray-based comparative genomic hybridization (arrayCGH) allows the construction of high-resolution genome-wide maps of copy number alterations, and statistical software packages are available for exploring and analysing array-CGH data (see, for example, [2,3]), facilitating the delineation of the boundaries of CNAs in individual tumors and thereby localizing and identifying potential oncogenes and tumor suppressor genes. The aim of this study was to evaluate the prognostic value of gene expression-based classification as well as established prognostic markers, including mutation status of the TP53 gene, in a group of breast cancer patients with long-term (>10 years) fol The aim of this study was to compare MR spectroscopic findings from breast cancer tissue with histological grading of tumor and patient lymph node status
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