Current Genomics - Volume 11, Issue 3, 2010

Breast cancer is a heterogeneous disease with a complex etiology that develops from different cellular lineages, progresses along multiple molecular pathways, and demonstrates wide variability in response to treatment. The “standard of care” approach to breast cancer treatment in which all patients receive similar interventions is rapidly being replaced by personalized medicine, based on molecular characteristics of individual patients. Both inherited and somatic genomic variation is providing useful information for customizing treatment regimens for breast cancer to maximize efficacy and minimize adverse side effects. In this article, we review (1) hereditary breast cancer and current use of inherited susceptibility genes in patient management; (2) the potential of newly-identified breast cancer-susceptibility variants for improving risk assessment; (3) advantages and disadvantages of direct-to-consumer testing; (4) molecular characterization of sporadic breast cancer through immunohistochemistry and gene expression profiling and opportunities for personalized prognostics; and (5) pharmacogenomic influences on the effectiveness of current breast cancer treatments. Molecular genomics has the potential to revolutionize clinical practice and improve the lives of women with breast cancer.

RNA interference (RNAi) screens have recently emerged as an exciting new tool for studying gene function in mammalian cells. In order to facilitate those studies, short hairpin RNA (shRNA) expression libraries covering the entire human transcriptome have become commercially available. To make use of the full potential of such large-scale shRNA libraries, microarray-based methods have been developed to analyze complex pooled RNAi screens. In terms of microarray analysis, different strategies have been pursued by different research groups, largely influenced by the employed shRNA library. In this review, we compare the three major shRNA expression libraries with a focus on their suitability for a microarray-based analysis of pooled screens. We analyze and compare approaches previously used to perform pooled RNAi screens and point out their advantages as well as limitations.

Over the second half of 20th century much research on lipogenesis has been conducted, especially focused on increasing the production efficiency and improving the quality of animal derived products. However, many diferences are observed in the physiology of lipogenesis between species. Recently, many studies have also elucidated the involvement of numerous genes in this procedure, highlighting diferences not only at physiology but also at the molecular level. The main scope of this review is to point out the major differences between ruminant and non ruminant species, that are observed in key regulatory genes involved in lipogenesis. Human is used as a central reference and according to the findinggs, main differences are analysed. These findings could serve not only as basis for understanding the main physiology of lipogenesis and further basic research, but also as a basis for any animal scientist to develop new concepts and methods for use in improving animal production and modern genetic improvement.

Damage to the genetic material can affect cellular function in many ways. Therefore, maintenance of the genetic integrity is of primary importance for all cells. Upon DNA damage, cells respond immediately with proliferation arrest and repair of the lesion or apoptosis. All these consequences require recognition of the lesion and transduction of the information to effector systems. The accomplishment of DNA repair, but also of cell cycle arrest and apoptosis furthermore requires protein-protein interactions and the formation of larger protein complexes. More recent research shows that the formation of many of these aggregates depends on post-translational modifications. In this article, we have summarized the different cellular events in response to a DNA double strand break, the most severe lesion of the DNA.

Similarly to metazoans, the budding yeast Saccharomyces cereviasiae replicates its genome with a defined timing. In this organism, well-defined, site-specific origins, are efficient and fire in almost every round of DNA replication. However, this strategy is neither conserved in the fission yeast Saccharomyces pombe, nor in Xenopus or Drosophila embryos, nor in higher eukaryotes, in which DNA replication initiates asynchronously throughout S phase at random sites. Temporal and spatial controls can contribute to the timing of replication such as Cdk activity, origin localization, epigenetic status or gene expression. However, a debate is going on to answer the question how individual origins are selected to fire in budding yeast. Two opposing theories were proposed: the “replicon paradigm” or “temporal program” vs. the “stochastic firing”. Recent data support the temporal regulation of origin activation, clustering origins into temporal blocks of early and late replication. Contrarily, strong evidences suggest that stochastic processes acting on origins can generate the observed kinetics of replication without requiring a temporal order. In mammalian cells, a spatiotemporal model that accounts for a partially deterministic and partially stochastic order of DNA replication has been proposed. Is this strategy the solution to reconcile the conundrum of having both organized replication timing and stochastic origin firing also for budding yeast? In this review we discuss this possibility in the light of our recent study on the origin activation, suggesting that there might be a stochastic component in the temporal activation of the replication origins, especially under perturbed conditions.

TWIST1 is thought to be a novel oncogene. Understanding the molecular mechanisms regulating the TWIST1 gene expression profiles in tumor cells may give new insights regarding prognostic factors and novel therapeutic targets in veterinary oncology. In the present study we partially isolated the TWIST1 gene in Felis catus and performed comparative studies. Several primer combinations were used based on the alignments of homologous DNA sequences. After PCR amplification, three bands were obtained, purified and sequenced. Several bioinformatic tools were utilized to carry out the comparative studies. Higher similarity was found between the isolated TWIST1 gene in Felis catus and Homo sapiens (86%) than between Homo sapiens and Rattus norvegicus or Mus musculus (75%). Partial amino acid sequence showed no change in the four species analyzed. This confirmed that coding sequences presented high similarity (∼96%) between man and cat. These results give the first insights regarding the TWIST1 gene in cat but further studies are required in order to establish, or not, its role in tumor formation and progression in veterinary oncology.