The AP-HM tissue bank is the largest one in France regarding some collections, including brain tumors. This collection was used to better characterize some gliomas. In particular because some benign gliomas such as pilocytic astrocytomas (WHO grade I) can be misclassified as malignant ones such as glioblastomas (grade IV) the first aim of our study was to find accurate diagnostic markers. This was done mainly by suppressive substractive hybridization (SSH). This study also provides a restrictive list of genes selectively involved in angiogenesis and invasion, which were highly expressed in GBM. Results were confirmed by real time quantitative RT-PCR in a large cohort of patients. In addition in order to find accurate markers which can predict GBM overall survival (OS) we selected three cohorts of GBM patients with distinctive OS (short survival < 6 months, long survival > 18 months and intermediate). Quantification of a series of markers involved in angiogenesis and invasion was done as well as cDNA array analysis.

ENT cancers in France - with the fourth rank after the breast, colon and prostate localizations - represent on important problem of public health. Survival at five years reaches a maximum in spite of undeniable therapeutic progress, in particular with the targeted treatments associated to conventional cytotoxic drugs. The studies in progress still make it possible to hope for new predictive and prognostic biological markers, but the complexity of these parameters, as well as the needs for heavy and expensive equipment to explore them, require a unification of the efforts and means. It is the major objective of the cooperative program PACOR.

Colorectal tumorigenesis is associated with the progressive increase of epithelium dysplasia and wall invasion. These criteria are evaluated through histological staging, that enables a reliable estimation of patient prognosis, and is the best tool for therapeutic decision. Adjuvant chemotherapy is systematically proposed in case of lymph nodes and/or distant metastases (stages III and IV respectively). Its benefit in stage II tumors however remains unclear. Independently of the nature of the treatment, one third of all stage II-III tumors will metastasize. One important element to improve our tools for therapeutic decision is the identification of prognostic parameters, independent of the histological and morphological classifications. In a preliminary study, we allelotyped a series of 401 colon tumors and have shown that 5q and 8p allelic status were significantly predictive of the patients evolution. As a first approach, analysis of 47 tumors using microarray expression measures has allowed to validate the strong correlation between RNA levels and genomic status (i.e. mutation and allelic status) of known genes (APC, SMAD4, TP53, MLH1). We are now planning to characterize a series of 185 stage II-III colon tumors at both genomic and transcriptomic levels, in combination with the clinicopathological findings. Disease-free patients were followed at least 3 years after surgical resection. A tight collaboration of 5 departments of digestive oncology allowed to collect all clinical and biological resources for this project. Depending on our findings, correlations will be made between gene expression levels and somatic mutations of the coreesponding genes. Real time RT-PCR and immunohistochemical analyses will be performed on selected genes. Finally, biological mechanisms will be investigated to look for new therapeutic targets.

The correct enumeration of human chromosomes, only established in 1956, has marked the starting point of the modern cytogenetics. The introduction of banding techniques, then of in situ hybridization techniques, and now of genomic microarray technology allowed a dramatic development of cytogenetics of which the main applications to basic and medical research are evoked in this review.

A cytological, immunophenotypical and cytogenetical study of 136 chronic B-cell proliferations (93 CLL, 43 B-cell lymphomas) was led in order to precise diagnosis and to characterize and appreciate chromosomal rearrangements. In this series, mainly selected on blood lymphocytosis criteria, B-CLL were twice more frequent than small B-cell lymphomas. Probes used revealed cryptic abnormalities, which remained unknown by conventional cytogenetics (CC). The frequency of clonal abnormalities (CC and FISH) was 74.8% for this series, with 74.4% for lymphomas and 75.3% for CLL, mainly of Binet stage A (69 A, 13 B, 1 C, 10 unspecified). Proportion was 88.4% in A stages and 84.6% in B stages. In CLL, 13q14 cryptic deletions and translocations were widely majority, 14q32 translocations and trisomy 12 being predominant in lymphoma series. Interphase FISH study of non-clonal metaphasic abnormalities with locus-specific probes often revealed unrecognised clones.

Gene regulation by transcriptional and post-translational mechanisms is implicated in the regulation of cellular homeostasis. Transcriptional deregulation has been largely documented in the etiology of diseases such as cancer, obesity and diabetes. During the past decade, the control of translation initiation by the PI3K/Akt/mTOR pathway in the development of these pathologies has been documented. Rapamycin, a specific inhibitor of mTOR, demonstrates considerable anti-proliferative activity against numerous cancer types. Recent studies also demonstrated that rapamycin may be beneficial in the treatment of obesity and diabetes. Rapamycin and its analogs seem destined for a promising future and will help in the development of novel therapeutic strategies.

Aptamers are short oligonucleotides selected from large combinatorial pools of sequences for their capacity to bind to many different targets ranging from small molecules (amino acids, antibiotics...) to proteins or nucleic acid structures. Aptamers present the same high specificity and affinity for their targets as antibodies. In addition to efficient binding, aptamers have been shown in many cases to display an inhibitory activity against their targets. Many aptamers are now being developed against biomedical relevant targets, and one aptamer that inhibits the human VEGF165 already received approval for the treatment of age-related macular degeneration. Here we discuss the principles and the practical way of selecting aptamers (SELEX technology) as well as the structural basis for their performance as ligands. A wide scope of applications is described - aptamers have been used as tools for studying nucleic acids/proteins interactions, detecting, purifying or imaging target molecules, regulating gene expression - and includes recent developments of aptamers for therapy and diagnosis.

The HNPCC syndrome (hereditary nonpolyposis colon cancer) is an inherited condition defined by clinical and genealogical information, known as Amsterdam criteria. In about 70% of cases, HNPCC syndrome is caused by germline mutations in MMR genes, leading to microsatellite instability of tumor DNA (MSI phenotype). Patients affected by the disease are at high risk for colorectal and endometrial carcinomas, but also for small intestine, urothelial, ovary, stomach and biliary tract carcinomas. HNPCC syndrome is responsible for 5% of colorectal cancers. Identification and management of this disease are part of a multidisciplinary procedure.

Since the last recommendations, up to 2500 new references had been published on that topic.

From differential analysis for the identification of biomarkers, to functional analysis for the evidencing of new therapeutic targets, proteomics brings new comprehensive information for a better understanding of the molecular basis of oncology and new perspectives for the clinic. However the major limitation of proteomic investigations and more generally of post-genomic approaches remains the molecular and cellular complexity of biological systems. This will be illustrated with the case of breast cancer.

The pathogenic mechanisms of polyvythemia vera (PV) still remain unknown, although there is evidence that genetic parameters may play a role in the pathogenesis of the disease.

The polycystic ovary syndrome (PCOS) is the most frequent cause of hyperandrogenism and anovulation in adult women as well as in adolescent girls. Since 2003 the diagnosis of PCOS has been based on the association of hyperandrogenism, oligoanovulation and polycystic ovary (PCO) morphology at ultrasound (at least 2 items out of 3). In adolescents however, PCOS features may be difficult to distinguish from the symptoms of the end of puberty. Moreover, transvaginal ultrasound examination is seldom possible, and it is difficult to get precise imaging of the ovaries by abdominal route. However, the diagnosis of PCOS in a hyperandrogenic and/or oligomenorrheic adolescent requires on the strict application of the Rotterdam criteria, as in adult women. Priority should be given to clinical features whereas pelvic ultrasound must be considered as optional. Few hormonal assays will serve mainly to make the differential diagnosis, in addition to clinical findings. Once established, the diagnosis of PCOS in an adolescent girl must lead to the detection of the metabolic syndrome by means of simple investigations. This will allow early prevention of its complications.