Sarcomas represent a heterogeneous group of tumors with a complex and poorly reproducible classification. However, in the last ten years, several specific genetic alterations have been described allowing a molecular classification with: 1) sarcomas with a specific translocation which can be used as a diagnostic marker. These translocations can be demonstrated by RT-PCR or by FISH with commercially available break apart probes ; 2) sarcomas with simple genomic profile showing amplification of a few genes. Well differentiated liposarcomas, dedifferentiated liposarcomas and intimal sarcomas show a simple genomic profile characterised by MDM2 and CDK4 amplifications associated with amplification of other genes in dedifferentiated liposarcomas ; 3) sarcomas with activating mutations: about 90% of GIST show activating mutation of a receptor tyrosine kinase gene, either KIT or PDGFRA. The most frequent mutation involves exon 11 of KIT followed by exon 9 of KIT and exon 18 of PDGFRA. Demonstration of these mutations is useful for the diagnosis of CD117 negative GIST, for predicting response to imatinib and to explain secondary resistance to imatinib ; 4) sarcomas with inactivating mutations: malignant rhabdoid tumors show biallelic inactivation of INI1 gene with a lost of INI1 expression which can be demonstrated by immunohistochemistry ; 5) other sarcomas usually show a complex genomic profile characterised by numerous gains and losses of genes with a frequent loss of RB1 and alterations of P53. Leiomyosarcomas, pleomorphic rhabdomyosarcomas, pleomorphic liposarcomas, myxofibrosarcomas, poorly differentiated sarcomas (so-called MFH and fibrosarcomas) belong to this category and show no specific molecular abnormality.

Genomic DNA displays a non canonical structure prone to be damaged and modified by genotoxic stresses, which are induced either by the endogenous metabolism or attacks from environment or therapeutic pressure. Several molecular pathways allow cells to repair such DNA lesions. Additional mechanisms have been selected to bypass such damage at the price of mutations. The maintenance of the genome is thus mediated by the respect of a balance between accurate and inaccurate DNA transactions. This review deals with the tumor suppressor role of such equilibrium, as well as the impact of an unbalance on carcinogenesis.

Von Recklinghausen's neurofibromatosis is a dominant autosomic genetic disease characterized by different clinical manifestations. The goal of this work was to study its orthopaedic manifestations and to show the characteristics of their management.

The discovery of oncogenes and tumor suppressors has established the original concept of cancer development based on a cascade of spontaneously occurring somatic mutations. It is now well known that genomes of cancer cells are deeply rearranged and that these rearrangements have devastating consequences on their organization and function. These rearrangements and their functional consequences are increasingly well characterized leading to the identification of numerous novel mutations, including a number of orphan mutations. The number of cancer genes has constantly been on the rise as a consequence of technological evolution. Starting from a couple of dozen founder genes, we are presently facing lists comprising several hundreds of genes. These correspond to genes affected by structural rearrangements or mutations, those modified at the epigenetic level and, more recently, miRNAs. The current challenge resulting from this brutal increase will be to sort out founder from passenger mutations and deduce the oncogenic cascades that correspond to each tumor phenotype.

Contrary to current belief, the concept of microRNA (miRNA) is quite old. Indeed, the first report on a small RNA able to control the translation of a specific messenger RNA (and therefore called translational control RNA or tcRNA) dates 35-year back. miRNAs waited until 1993 to be "rediscovered" and become the focus of an intense research activity which led to the discovery of several hundreds of them, to the unraveling of their biosynthesis and of their involvement in numerous physiological and pathological processes, notably in cancer. They represent another testimony to the crucial role plaid by RNA at all levels of gene expression regulation and dysregulation. If the old saying "the roots of cancer lie in our DNA" is still valid, one cannot anymore overlook, as has been the case for too long, that its role is not limited to the univocal expression of protein-coding messengers but rather that many downstream mechanisms exist to control and eventually dramatically alter their expression qualitatively (though alternative splicing) as well as quantitatively thanks to the miRNAs which are the topic of this review.

The genetic origins of the development of malignant haematological disorders have been established at the beginning of the 80ies. Systematic characterization of chromosomal structural abnormalities and, more recently by DNA microarray approaches and sequencing of tumour genomes have allowed the identification of a large number of genes that are mutated during malignant transformation in humans. Functional studies of these human oncogenes have shown that most of them were not able to transform a haematologic progenitor when acting alone and that cooperation with other oncogenic events was required. The present challenges are the evaluation of the role of each mutation in malignant transformation and the definition of the chronology of their emergence. From these data, the development of efficient therapeutic approaches will be possible by targeting the early oncogenic events which are at the origin of the malignant transformation.

The high heterogeneity of clinical, histological, biological and genetic features in breast cancer is due in part to the extreme molecular complexity of these tumors. This review article presents the major technological advances of the past ten years, in particular the development of microarray approaches, which have enabled genome-wide ("Omics") analysis of these tumors. Numerous genetic and epigenetic alterations involving a small number of altered signalling pathways (PI3K, NK-κB, FGF, etc.) have been described. The next decade will be even more prolific in terms of discovery with the advent of next-generation sequencing (NGS) technologies that will provide fast and low cost constitutional and somatic genome sequences. The full catalogue of somatic genetic alterations will result in a completely new individual management for breast cancer patients.

While no real improvement in the long term survival has been obtained in lung cancer, during this decade a significant improvement in cancer control has been obtained by biology driven targeted therapy as with anti EGFR tyrosine kinase. Two phases can be described in the knowledge of lung cancer biology: a first phase open in the 1980s describing the main molecular anomalies and impaired cell control mechanisms, and a second phase starting in the 2004-2005 giving rise to the therapeutic applications of this knowledge. A new molecular classification of lung cancer, particularly adenocarcinomas will soon be proposed for therapeutic application.

Senescence was originally described from the observation of the limited ability of normal cells to grow in culture, and may be generated by telomere erosion, accumulation of DNA damages, oxidative stress and modulation of oncogenes or tumor suppressor genes. Senescence corresponds to a cellular response aiming to control tumor progression by limiting cell proliferation and thus constitutes an anticancer barrier. Senescence is observed in pre-malignant tumor stages and disappears from malignant tumors. Agents used in standard chemotherapy also have the potential to induce senescence, which may partly explain their therapeutic activities. It is possible to restore senescence in tumors using targeted therapies that triggers telomere dysfunction or reactivates suppressor genes functions, which are essential for the onset of senescence.

A complex system of molecular milestones ensures labelling of the genome, driving its organization and functions. These milestones correspond to particular marks associated to active and repressed genes, as well as to non-coding regions or those containing repetitive sequences. Most of these marks are chemical modifications of DNA, corresponding to cytosine methylation, or various posttranslational modifications of histones, the proteins which package the genome. These chemical modifications of DNA or histones are reversible and are catalysed and removed by enzymatic activities associated with factors ensuring critical cellular functions. Indeed, these enzymes are directly connected with signalling pathways, sensing extra- and intracellular environments. Altogether these mechanisms globally control the expression status of genes in each cell, meaning that certain genes are kept active, while most of the genome remains silent. Subtle metabolic changes or intra and extracellular modifications, by altering the marking associated to genes, can have long-term consequences on their expression status. Genes coding for essential regulators of cellular proliferation and differentiation could be among these genes, such as tumor suppressor genes for instance. Hence the knowledge of all these so-called "epigenetic" mechanisms will shed new light on the environmental impact on the control of gene expression and associated diseases, including malignant transformation. The understanding of these mechanisms will also pave the way for innovative therapeutic strategies to fight cancer. This review is aiming to give an overview to the reader of the relevance of epigenetic mechanisms for the understanding and treatment of cancer.