We report a case of spontaneous hemothorax in a 9-year-old boy due to costal exostosis in the context of hereditary multiple exostosis disease. This is an unusual complication, whose pathophysiology remains unclear.

The College of General Hospital Respiratory Physicians (CPHG) is following up the KBP-2000-CPHG study, performed ten years ago, with a new observational epidemiological study of primary lung cancer.

To detect major chromosomal aberrations from enucleated uveal melanoma and relate them to hepatic metastasis and survival.

In urologic oncology, prostate cancer represented, even this year, a wide part during the ASCO 2010 meeting. In the non metastatic diseases, two phase III trials confirmed the benefit of radiotherapy combined with hormonotherapy in locally advanced stage. For patients with metastatic hormonoresistant cancer, two randomized trials will probably change the daily practice in the next months. On the one hand, denosumab versus zoledronate decreased significantly the risk of skeletal-related events in bone metastases. On the other hand, compared with mitoxantrone, cabazitaxel in docetaxel pretreated patients improved overall survival. On the contrary, docetaxel in monotherapy remains the standard of care in first line chemotherapy in castration refractory metastatic prostate cancer. Indeed, in two trials, combination of bevacizumab or calcitriol with docetaxel showed no benefit for patients with more toxicities. Finally, docetaxel-based chemotherapy was again evaluated in two other situations: biological recurrence, and hormono-sensitive metastatic stage. Preliminary results of tolerance were presented this year. No doubt that communications during future ASCO meetings would reported definitive results of efficiency of these phase III studies.

Widespread screening for prostate cancer has led to an increased incidence, an improved disease specific survival, but also to overdiagnosis and overtreatment. The limitations of screening tools, especially PSA, have led to active investigation of new biomarkers in recent years. Urinary markers, suitable for large scale use, minimally invasive collected, arouse of particular interest. Numerous protein, DNA or RNA markers are explored in order to improve detection and prognostic evaluation of prostate cancer. Some of them have already shown clinical values. PCA3 provided particularly encouraging results for the specific population of patients having a first set of negative biopsy, for which using PCA3 assay could allow to avoid unnecessary repeated biopsy. Fusion genes showed promising abilities in prostate cancer detection. New research methods are also emerging, and high-throughput technologies will facilitate high-dimensional biomarker discovery. Future approaches will probably integrate proteomic, transcriptomic and multiplex approaches to identify combinations of multiple biomarkers to optimize the detection of prostate cancer. In the near future, these markers would probably be able to provide prognostic data to discriminate significant cancers, a major challenge for prostate cancer treatment.

Glial tumors represent 2000 to 3000 new cases per year in France and 75% of them are of high grade. Recent understanding of the molecular biology of these tumors revealed the importance of 1p19q codeletion and mgMT promotor methylation. Radiotherapy also recently evolved with the progress in medical imaging which allows a better definition of the target volumes. Even modest, therapeutic progress is based on chemoradiotherapy with temozolomide and on the development of non-coplanar conformational radiotherapy. Knowledge and precise evaluation of potential late effects of our treatments is necessary due to actual improvement of survival with chemoradiotherapy in glioblastoma.

Recent progress in the field of molecular biology has allowed us to identify at least two different molecular mechanisms implicated in colorectal carcinogenesis (CRC): chromosomal instability (CIN) and genetic instability. Even though the two molecular mechanisms differ, their signalling pathways, implicated in malignant transformation of colonic epithelial cells, appear to be similar. The most frequent group of CRC, which represents 80% of sporadic CRC, is characterized by allelic losses on the short arm of chromosome 17 and 8 and on the long arm of chromosome 5, 18 and 22. These allelic losses are associated with mutations in TP53, APC, SMAD2 and SMAD4 genes. All of these alterations are grouped under the phenotype CIN. A genetic instability termed MSI (microsatellite instability), which results from a mismatch repair (MMR) deficiency, appears in 12-15% of CRC cases. The presence of MMR deficiency leads to the accumulation of mutations in genes controlling cell cycle and apoptosis (TGFBRII, BAX or CASPASE5). More recently, the existence of a third phenotype was suggested. The main alteration associated with this group of tumors is the hypermethylation of the promoter region of numerous genes, leading to their inactivation. An activating mutation of BRAF is frequently associated with this phenotype. As described above, CRC shows genetic heterogeneity, however the consequences in terms of signalling pathway alterations are similar. For example, the activation of Wnt signalling pathways can result from the inactivation of the APC gene in the CIN phenotype or from an activating mutation in the β-catenin gene in MSI tumors. The inactivation of TGFβ pathways is also present in both tumor types and is driven by SMAD4, and more rarely by a SMAD2 inactivating mutation in CIN tumors, or by the existence of a frame-shift mutation occurring in a polyG coding track of the TGFβ (transforming growth factor) receptor type II in MSI tumors. The RAS-MAP kinase pathway is activated by KRAS mutations in CIN tumors or by BRAF mutations in MSI tumors. The p53 pathway is inactivated by TP53 inactivation in CIN tumors or by BAX inactivating mutations in MSI tumors.

Cancers can be considered as gene diseases. A number of mechanisms leading to cancer have been identified through the discovery of structural alterations of genes called 'oncogenes' and 'tumour suppressor genes'. Somatic and germinal mutations are rare but play a determinant role in the emergence of cancer, while common and frequent variations (polymorphisms) play a role in cancer susceptibility and in the effects of anticancer drugs (efficacy and toxicity). After a general overview on the structural and functional organisation of the human genome, we present here some of the techniques aimed at the identification of structural DNA variations. We present afterwards some examples of the role that play polymorphic constitutive variations of the genome in the occurrence of cancer (molecular epidemiology) and the activity of anticancer drugs (pharmacogenetics).

This presentation reports a series of data dealing with recurrent genetic abnormalities and gene expression profiles that characterize primary glioblastomas and secondary glioblastomas resulting from the transformation of low grade tumors (grade II and III astrocytomas and oligodendrogliomas). The most recent aspects of the concept of tumor stem cells that may explain the relentless growth of GBM will be reported. Molecular features of tumor neoangiogenesis will be described. Epigenetic alterations and deregulation of gene expression by microRNAs (miRs) will be also included. Some aspects of tumor predisposition will be also discussed. Finally, a short description of exosomes as vectors of tumor information will be presented.

Numerous molecular abnormalities have been described in lymphomas. They are of diagnostic and prognostic value and are taken into account for the WHO classification of these tumors. They also shed some light on the underlying molecular mechanisms involved in lymphomas. Overall, four types of molecular abnormalities are involved: mutations, translocations, amplifications and deletions of tumor suppressor genes. Several techniques are available to detect these molecular anomalies: conventional cytogenetic analysis, multicolor FISH, CGH array or gene expression profiling using DNA microarrays. In some lymphomas, genetic abnormalities are responsible for the expression of an abnormal protein (e.g. tyrosine-kinase, transcription factor) detectable by immunohistochemistry. In the present review, molecular abnormalities observed in the most frequent B, T or NK cell lymphomas are discussed. In the broad spectrum of diffuse large B-cell lymphomas microarray analysis shows mostly two subgroups of tumors, one with gene expression signature corresponding to germinal center B-cell-like (GCB: CD10+, BCL6 [B-Cell Lymphoma 6]+, centerine+, MUM1-) and a subgroup expressing an activated B-cell-like signature (ABC: CD10-, BCL6-, centerine-, MUM1+). Among other B-cell lymphomas with well characterized molecular abnormalies are follicular lymphoma (BCL2 deregulation), MALT lymphoma (Mucosa Associated Lymphoid Tissue) [API2-MALT1 (mucosa-associated-lymphoid-tissue-lymphoma-translocation-gene1) fusion protein or deregulation BCL10, MALT1, FOXP1. MALT1 transcription factors], mantle cell lymphoma (cycline D1 [CCND1] overexpression) and Burkitt lymphoma (c-Myc expression). Except for ALK (anaplastic lymphoma kinase)-positive anaplastic large cell lymphoma, well characterized molecular anomalies are rare in lymphomas developed from T or NK cells. Peripheral T cell lymphomas not otherwise specified are a heterogeneous group of tumors with frequent but not recurrent molecular abnormalities. Gene profiling analysis shows that the expression of several genes is deregulated including PDGFRA (platelet-derived growth factor receptor) gene, encoding a receptor with tyrosine kinase activity. In angio-immunoblastic T-cell lymphomas molecular abnormalities are found in follicular helper T-cell (TFH) that express some distinctive markers such as CD10, PD-1, CXCR5 and the CXCL13 chemokine. ALK-positive anaplastic large cell lymphoma is a paradigme of T-cell lymphoma since it is associated with an X-ALK oncogenic fusion protein due to a translocation involving ALK gene at 2p23. ALK tyrosine kinase activates downstream pathways (Stat3/5b, Src kinases, PLCγ, PI3 kinase) implicated in lymphomagenesis, proliferation and protection against apoptosis. Specific ALK inhibitors are currently in clinical evaluation. Lastly several lymphomas are associated with infectious agents that play a direct (EB virus, HTLV1) or indirect role (e.g. Helicobacter pylori in MALT lymphoma) in lymphomagenesis.