Ewing's tumour is the second most frequent primary tumour of bone. It is associated in 85% of cases with a specific and recurrent chromosome translocation, a t(11; 22)(q24; q12) which generates a fusion gene between the 5' part of EWS and the 3' part of FLI-1, a member of the ETS family. Less frequently, this gene fusion involves EWS and another member of the ETS family which can be: ERG, ETV1, E1AF or FEV depending on the cases. The EWS-ETS fusion is causative in the development of Ewing's tumour. Its mechanism of action mainly relies on the abnormal transcription regulation of key target genes which are involved in the regulation of cell cycle, signal transduction, migration. The cellular context within which EWS-FLI-1 exerts its oncogenic action is a long standing matter of debate. Recent data converge to suggest that the Ewing cell origin is a mesenchymal stem cell.

Living organisms can be seen as complex chemicals interacting with their environment through chemical reactions. As such, they are subjected to the laws of stoichiometry: their constitutive elements (atoms) cannot be created (they must be found in their environment) nor destroyed. Acknowledging these rules led ecologists to the concept of "biological stoichiometry". In this review, I want to show that combining (1) the study of the elemental composition of biopolymers and (2) the ecologist's point of view, particularly the concept of biological stoichiometry, benefits molecular biology. In particular, this coupled approach unveils parts of the history of organisms, helps interpreting transcriptional profiles and sheds a different light on the growth of carcinogenic tumors.

Ex vivo cutaneous gene therapy is an alternative treatment for recessively inherited diseases with cutaneous traits. It relies on the transfer in cultured epidermal keratinocytes of the wild-type allele of the gene whose mutation is responsible for the disease. As for severely burnt patients, epithelial sheets developed from genetically corrected cells may then be grafted back to the patients. Long term correction and graft take depend on the genetic correction of stem cells. Success of such an approach has recently been reported in the case of one patient suffering from a severe case of junctional epidermolysis bullosae. Here we report a method for safely selecting keratinocytes populations after genetic manipulation. The method is non invasive and non immunogenic and allows high enrichment of genetically manipulated stem keratinocytes. This could perhaps contribute to ex vivo gene therapy approaches of cancer prone genodermatoses such as xeroderma pigmentosum.

Waldenström macroglobulinemia (WM) is now defined as an uncommon lymphoplasmocytic proliferation associated with an immunoglobulin M peak. The associated chromosomal abnormalities are not specific to the disease, and changes in the diagnostic criteria and techniques used as well as low-level abnormal cell proliferation made their analysis difficult. A literature review however, shows that if specific abnormalities were not recognized until now, it is the frequency of some chromosomal abnormalities (for instance partial deletion of the long arm of chromosome 6 and trisomy 4) that distinguishes WM from other chronic malignant B-cell proliferations. The data collected in the present review show directions for future research which will benefit from use of more recent techniques such as fluorescent in situ hybridization, comparative genomic hybridization and expression microarrays.

Amplification of the HER2 gene, mapping to 17q21.1, is present in about 20 % of breast carcinomas. Amplification leads to an overexpression of the protein that made it possible to develop a targeted therapy by the monoclonal antibody trastuzumab (Herceptin). A good response to the treatment requires a stringent assessment of the gene status in tumours; only patients whose tumour shows a high expression of the protein or an amplification of the gene are eligible. Cases with intermediate level expression are checked by in situ hybridization, mainly by FISH, to identify amplifications in this subset of tumours. Results are sometimes difficult to interpret due to the frequent aneuploidy of the tumours. Moreover, copy number cut-offs of the gene for defining an amplification are variable according to the studies. A tumour is considered now as amplified when showing more than six HER2 copies per nucleus, or a ratio HER2 to centromere 17 greater than 2.2. The phenomenon of HER2 amplification in breast cancers is discussed in this paper, and distinguished from gene overrepresentation. It is recommended that tumours showing six to seven copies of HER2 are assessed with a kit including the centromere 17. Clusters of signals are characteristic of amplifications. The process designed for the assessment of HER2 is a model of strategies that will be used for the evaluation of markers involved in future targeted therapies.

Therapeutic control of primary or secondary hypertension remains insufficient because of the presence of individual phenotypic variations of factors acting on sodium excretion and vasoconstriction. The study of monogenic models of hypertension allows to highlight some genetic mutations, mainly responsible of sodium regulation. In some cases, polymorphisms of such genes are found with an increased frequency in hypertensive patients. Each polymorphism by itself is not sufficient to cause hypertension, but their accumulation in a patient increases the hypertensive risk in primary or secondary hypertension. Understanding familial hyperaldosteronism type 1, Liddle or Ulick syndrome, activating mutations of minéralocorticoide receptor or Gordon syndrome give indications on pathophysiology of primary hypertension. Study of some mitochondrial defects or of genes implicated in renal dysplasia also seems interesting area of research. In the future, search for such mechanisms would allow a rational and oriented use of diuretics and antihypertensive therapies.

Alport syndrome is a rare progressive hematuric nephropathy associated with sensorineural deafness. Leiomyomatosis associated with Alport syndrome is quite rare. We report a particular case of Alport syndrome which was diagnosed in the setting of an oesophageal leiomyomatosis. Alport syndrome and leiomyomatosis are caused by mutation of the genes encoding for the alpha chain of type IV collagen. In view of the important clinical and genetic implications, renal function and urinary status should be controlled in any patient with oesophageal leiomyomatosis.

Mast cell disorders are defined by an abnormal accumulation of tissue mast cells in one or more organ systems. Clinical symptoms in mastocytosis result from mast cells derived mediators and, less frequently, from destructive infiltration of mast cells. Systemic mastocytosis is regressive among children, whereas the disease is persistent among adults. A clonal haematological non-mast cell lineage disease can be associated. The clinical course in these patients is variable ranging from asymptomatic for years to highly aggressive and rapidly devastating. Until recently, the only treatment of this incurable disease was symptomatic.

The telomeres protect the end of chromosomes from being recognized and processed as an accidental double stranded break. In human somatic cells, telomeres shorten progressively with every round of DNA replication, leading to dysfunctional telomeres that trigger cellular senescence or apoptosis depending on the cell type. This telomere erosion appears to play a role in cell renewal, ageing and cancer. Two recent studies demonstrated in mouse that eroded telomeres in cancer cells blocked for apoptosis limit cancer formation by triggering senescence. These results suggest that provoking senescence may provide a way to cure cancer and point to new therapeutical strategies targeting specific telomeric functions. Nevertheless, an important question remains unanswered: does replicative senescence limit tumor formation in human?

To regulate the spatiotemporal expression of their target genes, the transcription factors undergo post-translational modifications of which the most studied is phosphorylation. Acetylation and ubiquitinylation on lysine residues also exert a role in the transcription, as it is the case for the regulation of the activity of the huge family of Ets transcription factors. Recently, sumoylation, a post-translational modification similar to ubiquitinylation, was described as playing a crucial role in the inhibition of the activity of these factors.

Identification of new prognostic factors for colon cancer with no lymph node involvement may improve the selection of patients for adjuvant chemotherapy. The aim of this study was to assess the possibility of using gene expression profiling for this purpose. Fifty patients operated on for stage II colon cancer were included. Twenty-five of these patients relapsed, while the other 25 remained disease-free for at least 5 years. MRNA was extracted from fresh-frozen biopsies and hybridized to the Affymetrix GeneChip HGU133A. One thousand six hundred random splits of the 50 patients into a training set and a validation set were considered. For each split, a prognostic combination was derived from the training set (selection of the 30 genes most differentially expressed between patients who recurred and those who did not, by linear discriminant analysis), and its prognostic performance was assessed with the validation set. On average, accuracy was 76%, sensitivity 85%, and specificity 68%. A total of 6,124 genes were included in at least one of the 1,600 predictive combinations, and 55 genes were included in more than 100 combinations. This study supports the possibility of predicting the prognosis of non-metastatic colon cancer by tumor gene expression profiling. It also shows the highly variable gene composition of predictive combinations.

This review reports recent observations concerning specificities of the cellular energy metabolism in cerebral tissues that highlight on characteristics of that of glial tumours, such as the association of metabolic alterations aggressiveness of these tumours. Compared to normal cerebral tissue, glial tissue exhibits both a relative independence towards oxygen and substrate furnitures and thus vascularization, as well as the metabolic co-operation of neurons and glial cells within the tumour. Occurrence of a Warburg effect could explain such metabolic autonomy that might be associated to genetic changes observed in gliomas. Characteristics of the glycolytic metabolism within glioma tissue therefore may be novel land therapeutic approaches for the treatment of these tumours.

Gene expression analysis has many applications in the management of cancer, including diagnosis, prognosis, and therapeutic care. In this context, the reverse transcription quantitative polymerase chain reaction (RT-qPCR) has become the "gold standard" for mRNA quantification. However, this technique involves several critical steps such as RNA extraction, cDNA synthesis, quantitative PCR, and analysis, which all can be source of variation. To obtain biologically meaningful results, data normalisation is required to correct sample-to-sample variations that may be introduced during this multistage process. Normalisation can be carried out against a housekeeping gene, total RNA mass, or cell number. Careful choice of the normalization method is crucial, as any variation in the reference will introduce errors in the quantification of mRNA transcripts. By reviewing the different methods available and their related problems, the aim of this article is to provide recommendations for the set up of an appropriate normalisation strategy for RT-qPCR data in oncology.

The principal mission of the Breast International Group (Big), Transbig, and the Breast European Adjuvant Study Team (Breast), all located at the Jules Bordet Institute in Brussels, is to accelerate and facilitate the initiation and conduct of large and difficult breast cancer clinical trials. This is made possible through the excellent network of research groups, scientists, physicians and many other collaborators deeply committed to academic clinical and translational research. A clear example of this collaboration is the HERA trial (Herceptin Adjuvant trastuzumab in HER2 positive early breast cancer) that contributed to a change of clinical practice and improved the prognosis for this particular patient population. In addition, there is an important new generation of adjuvant trials, for example, Mindact, which is evaluating the use of microarray technology in treatment decision making, and the Altto and Neo-Altto studies, which have just started and are evaluating lapatinib, a small tyrosine kinase molecule given either adjuvantly or neo-adjuvantly, alone, sequentially or in combination with trastuzumab, in patients with HER2 positive early breast cancer. The latter studies, with their strong translational research component, aim to determine which tumour profiles will best benefit from lapatinib as opposed to treatment with trastuzumab alone.

HER-2 and potentially topoisomerase II alpha are clinically useful parameters in breast cancer. The gene status and protein expression are, for both markers, used as predictive markers in research or clinical practice. New guidelines for HER-2 testing from ASCO and CAP have been recently published and new definition for HER-2 gene amplification will probably decrease the impact of polysomy 17 on HER-2 FISH status evaluation. Different forms of HER-2 receptor (p95HER-2, p185HER-2) could be considered as prognostic or predictive markers in the future if preliminary results are confirmed. The topoisomerase II alpha case is more complex as the results of preclinical and clinical studies seem to be contradictory. The results of the clinical studies are so far, encouraging but need to be confirmed. Moreover studies should be designed to define which one of the protein or the gene or both should be evaluate as predictive markers of response to anthracyclines chemotherapy. More studies are needed today to consider this marker for daily practice.

The microarray technology has enabled scientists to simultaneously investigate the expression of thousands of genes. Regarding breast cancer, this technology has provided a molecular classification into clinically relevant subtypes, new tools to predict disease outcome and response to treatment and new insights into carcinogenesis and metastatic progression pathways. Here we describe the state of the art of gene expression profiling for breast cancer, and we discuss the potential impact on breast cancer patient management considering its limits and promises.