Meanwhile first gene therapy assays in cerebral gliomas are in progress, we present in this article a review of the major genetic aberrations reported to date in these tumors. The analysis of these alterations enabled, these last few years, significative advances in the understanding of the mechanisms involved in glioma tumorigenesis. It is now well recognized that tumors result from a multistep process requiring in particular proto-oncogenes activation and tumor suppressor genes inactivation. The different genes implicated in the development of gliomas, their place in the tumoral progression and their potential therapeutic relevance are detailed in this review. The continuation of the identification of glioma altered genes is essential to provide new diagnostic and pronostic markers, and specific targets for more efficient therapy.

Acute leukemia in neonates is rare and is more severe than leukemia in childhood.

Familial pheochromocytoma is an uncommon form of this neoplasia. It is characterized by an autosomal dominant inheritance and multicentric locations. It is more frequently encountered in children, but with a smaller risk of malignant transformation than in adults. The familial form may be associated with other disorders, particularly with multiple endocrine neoplasia (MEN), Von Hippel-Lindau's disease and Von Recklinghausen's disease. We report the case of a nine-year-old boy with multiple familial pheochromocytoma in whom sonography allowed to demonstrate five localizations.

Management of a patient with a diagnosed choroid plexus cyst (CPC) is probably one of the most difficult of all prenatal diagnostic problems. Similarity between the risk of chromosomopathy due to the appearance of CPC only and the risk of fetal mortality due to amniocentesis (both being about 1/200) is such that an individual approach must be adopted in each case. The couple must be given a full explanation of all the details, which will enable them to finally decide whether a conservative attitude is appropriate or, on the contrary, if a specific diagnosis should be sought by amniocentesis.

Therapeutic gene transfer for cancer can aim at different goals, the main of them being: 1. to increase anti-tumor cell immune response; 2. to introduce a drug-activating gene into tumor cells; 3. to normalize cell cycle by inhibiting oncogenes or transferring antioncogenes. Significant, sometimes spectacular results have been reported using models of transplantation of tumor cell lines to animals, but not yet with spontaneous animal tumors. Although most of the about 130 clinical trials of gene therapy authorized around the world are devoted to cancer, it is so far impossible to predict the future of this strategy, and when, if any, it will succeed.

The metastatic dissemination is one characteristic property of malignant tumors. It represents a crucial step in the progression of the disease. Multiple cellular and molecular mechanisms are involved in the dissemination of cancer cells and their proliferation at secondary sites. The metastatic process requires the transient or permanent acquisition of invasive properties mediated in part by diverse families of proteases. Numerous growth factors control the autocrine or paracrine growth of the tumor. These factors can also act as motogens and may contribute to the maintainance of the loss of the differentiated state of tumors. Angiogenesis of newly formed primary tumors is required for further growth and dissemination. Malignant cells modulate their adhesive status throughout the different steps of dissociation from the primary tumor and their intravasation and extravasation from lymph and blood vessels. Proteases, adhesion molecules, growth factors, angiogens and their cognate receptors may constitute markers to assign a metastatic phenotype and could serve as targets for the management of patients.

Apoptosis is a mode of active cell death having distinct biochemical and morphological features including chromatin condensation, polynucleosomal DNA fragmentation, and disruption of cells into apoptotic bodies. The apoptotic process plays a major role both during development and in the functioning of the immune system. Apoptosis may in part be genetically regulated, and may also be linked to physiological and non physiological signals from the environment. Apoptosis may be a defense at the cellular level against cancer. Moreover, there is evidence that a number of pro-oncogenes and tumor suppressor genes are involved in regulating apoptosis. Further understanding of the molecular events underlying the apoptotic process should provide new insights into the mechanism of tumorigenesis and facilitate the development of new strategies for the treatment of cancer.

Multiple mutations are present in most human tumours. These genetic modifications appear to be necessary to produce and select pretumoral, tumoral and metastatic clones. These multiple mutations can be sequentially produced by genotoxic agents leading to cancers with a long latency period or due to mutations in genes implicated in the control of the genetic stability. Several human diseases are linked with a very high cancer incidence because they are hereditarily carrying a mutation on some DNA repair genes, mismatch repair genes or tumour suppressor genes. These abnormal functions will produced a mutator phenotype leading to a cascade of genetic modifications which will allow the rapid production of cancer cells.

In less than ten years, the study of inherited conditions predisposing to cancer led to major discoveries on the basic mechanisms of carcinogenesis. Those investigations have permitted to discover a new class of cancer genes now named "suppressor" genes (or antioncogenes), and to demonstrate their implication in the majority of cancer including the sporadic one's. Those studies have indicated that familial forms of cancer can also result from alterations of a set of genes controlling genomic stability. In clinical practice, the identification of the molecular basis of major forms of inherited predisposition to cancer, has allowed to better define those cancer syndromes. As a consequence, it is now possible to propose to the at risk individuals, and their families, screening protocols based on precise estimate of their genetic risk.

Oncogenes have been discovered through the study of oncogenic retroviruses. Viral oncogenes present in the viral genome are the genes responsible for the transforming properties of these viruses. Viral oncogenes are altered forms of cellular genes, designated as proto-oncogenes, that have been transduced into the genome of transforming retroviruses. Deregulated expression or structural alteration of cellular proto-oncogenes by amplification, mutation or translocation has been implicated in the occurrence of human cancers.

The use of in vitro cell transformation, as a complement to the direct study of tumors and established tumor cell lines, has enabled the analysis of the contribution of diverse genes to the tumor phenotype. The most recent results have underlined the importance of fundamental mechanisms regulating cell proliferation. The role in the long term survival of mammalian cells in culture and in tumor progression of the telomerase enzyme, which permits the maintenance of chromosome ends integrity, has now been demonstrated. Cell cycle progression and its regulation are ensured by a positive control exerted by cyclin-kinase complexes and by a negative one exerted by kinase inhibitors. Cyclin and kinase genes are frequently altered in transformed and tumor cells, as well as the genes coding for membrane proteins responsible for cell-cell and cell-matrix contacts.

Dexamethasone-sensitive hyperaldosteronism is associated with early onset hypertension and primary hyperaldosteronism. Diagnosis is difficult but can be improved by genetic testing for the mutant gene.

Because of a family history of breast cancer, a 51-year-old patient underwent bilateral subcutaneous mammectomy in 1988. In February 1994 she presented with a nodule in the supramedial quadrant on the left. Needle biopsy suggested galactophoric adenocarcinoma which was confirmed histologically. A 1.5 cm tumour was removed together with a 3 cm reliquat of glandular tissue. Twelve axillary nodes were dissected and were found to be free of neoplastic infiltration. Hormone receptors were positive. Post-operative radiotherapy was performed. The outcome is unchanged at 6 months. Bilateral subcutaneous mammectomy can be proposed as a preventive measure in patients at risk, but as demonstrated by this case, exeresis is usually incomplete. The level of protection actually achieved is thus questionable. Clinicians should be aware of the risk of breast cancer developing after such elective operations since early screening programmes and the development of genetic methods based on the search for BRCA1 and BRCA2 genes will undoubtedly increase the number of patients requesting preventive measures.

Flow cytometry technic was used to study DNA synthesis of Hep G2 cells following mitomycin C and adriblastine treatments during 24 hours. DNA synthesis was expressed by 2 methods: the new expression global DNA synthesis (S+G2)/G1 that considered the cells during scheduled and unscheduled DNA syntheses of S and G2 phases and the cell cycle (Fox program) that evaluated the cells during scheduled DNA synthesis by the terms G1 = 2n, S = 2n+x and G2 = 4n which excluded unscheduled DNA synthesis. The experimental data treated with this new expression led to the determination of threshold concentrations for the two tested compounds where the DNA repair mechanisms were overloaded, leading to cell death. This term was shown to be more accurate to describe the genotoxic action of compounds. Furthermore, these threshold concentrations of DNA damages was found to be linked with significant increase of micronuclei in the micronucleus test.

Prostate cancer is one of the most common malignancies in men. Few authors have attempted to identify consistent genetic alterations at the molecular level in adenocarcinoma of the prostate, but those most frequently reported are loss of heterozygosity (LOH) involving chromosome arms 8p, 10q, 16q, and 18q and inactivation of the TP53 tumor suppressor gene. In order to determine if alterations frequently found in other adenocarcinomas (breast, ovarian, colorectal), including losses of genetic material from chromosome arms 1p, 3p, 7q, 8p, 11p, 17p, 17q, and 18q, are also involved in prostate cancer, we examined 20 localized early-stage prostate tumors. We detected no mutations of the TP53 gene. Allelic losses were found from 7q (33%), 8p (50%), 10q (20%), and 18q (33%). Furthermore, as the first step toward isolating tumor suppressor genes on 18q, we used six polymorphic markers and identified a small common deleted region between the chromosome 18 centromere and the D18S19 locus.

The orientation of the medical activity toward preventive strategies knows currently an important development. This movement shows various logic, which are: on one hand a rational step, a strategic choice in favour of prevention, and on the other hand a choice by elimination, when the other forms of intervention establish insufficient efficiency. Prevention had to follow the path of validity to acquire pertinence. The gold-standard is randomised blinded trials and it is this kind of procedure that has been proposed in the BCPT (Breast cancer prevention trial). By comparison with a classic therapeutic trial the main differences of prevention trial lay in: criteria of inclusion, analyses of impact larger than the simple efficiency (quality of life), on the focus on the risk (especially genetic) and the legal context. One of the main points is the question of risks induced by an intervention on healthy persons. In this context, even the passage of an uncertainty to a "certainty" concerning induced risks can not always suffice to close the controversy. Physicians cannot in this case, refer to norms and to models since this type of intervention is new.

During the spring of 1993, UKCCCR prevention trial group proposed to the french medical community to participate into the international breast cancer prevention trial by tamoxifen set up in Great Britain. In January 1994 this proposal was eventually judged unacceptable in France because of lack of reflexion on primary cancer prevention, medico-legal risks, tamoxifen use risks and the eligibility criteria. A randomized trial could be designed and carried out in France to evaluate the place of tamoxifen in breast cancer prevention in the following settings: post menopausal patient with atypical epithelial hyperplasia or lobular in situ carcinoma.

Branchio-oto-renal syndrome is an inborn disease of autosomal dominant transmission and variable expression. The syndrome associates ear pits, branchial cleft fistulas or cysts, deafness and renal anomalies heavily compromising prognosis. We report four adults (2 males, 2 females) in three different families with branchio-oto-renal syndrome. All 4 probands were seen for renal failure, with hematuria in 2 and proteinuria in the 2 others. Among the 62 family members examined 19 had at least one sign of branchio-oto-renal syndrome. Four pregnancies were followed during the course of the study, only one reached term. The frequency of branchio-oto-renal syndrome is probably underestimated. Prevalence has been estimated at 1/40,000 births. It accounts for 2% of the cases of severe deafness in children. Neck and ear morphology should therefore be carefully examined in patients with renal or urinary tract dysplasia. Women with a mild form of the disease with moderate renal failure may give birth to an infant with very severe renal failure leading to death either in infancy or in utero due to severe renal agenesia or hypoplasia.