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Open Access

High-density screening of the Zbtb7gene in breast cancer patients

  • A Salas1, 2,
  • A Vega2, 3,
  • M Torres2,
  • I Quintela2,
  • C Phillips2,
  • R Rodríguez-López4,
  • G Rivas4,
  • J Benítez4 and
  • A Carracedo1, 2, 3
Breast Cancer Research20057(Suppl 2):P1.22

https://doi.org/10.1186/bcr1109

Published: 17 June 2005

Keywords

Breast CancerBreast Cancer PatientBreast Cancer RiskBreast CarcinomaSpanish Patient

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.

Declarations

Acknowledgments

This work was supported by grants from the Ministerio de Sanidad y Consumo (Fondo de Investigación Sanitaria; Instituto de Salud Carlos III, PI030893; SCO/3425/2002) and Genoma España (CeGen; Centro Nacional de Genotipado; Nodo Santiago de Compostela).

Authors’ Affiliations

(1)
Unidade de Xenética, Instituto de Medicina Legal, Facultad de Medicina, Universidad de Santiago de Compostela, Galicia, Spain
(2)
Centro Nacional de Xenotipado, Hospital Clínico Universitario, Santiago de Compostela, Galicia, Spain
(3)
Fundación Pública Galega de Medicina Xenómica, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Galicia, Spain
(4)
Departamento de Genética Humana, Centro Nacional Investigaciones Oncológicas, Madrid, Spain

References

  1. Maeda T, Hobbs RM, Merghoub T, Guernah I, Zelent A, Cordon-Cardo C, Teruya-Feldstein J, Pandolfi PP: Role of the proto-oncogene Pokemon in cellular transformation and ARF repression. Nature. 2005, 433: 278-285. 10.1038/nature03203.View ArticlePubMedGoogle Scholar
  2. Cancer Genome Anatomy Project. [http://cgap.nci.nih.gov/Chromosomes]

Copyright

© BioMed Central 2005

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