The cytokinesis-blocked micronucleus assay (CBMN) is a short-term mutagenesis test which offers an easier and less tedious alternative to metaphase chromosome analysis, with the advantage that exposure to both clastogens and aneugens may be detected. The CBMN assay has been used in evaluating the genotoxic consequences of exposures to environmental and occupational mutagens and carcinogens. Micronucleated cell rates (MN cell rates) were assessed in cytokinesis-blocked lymphocytes of 70 male and female cancer patients prior to any anticancer treatment. The study of interindividual variation factors showed that only age significantly affect MN cell rate, whereas sex, tobacco, alcohol, imaging techniques and tumour stage had no significant effect. The comparison of micronucleated cell rates in 198 healthy subjects and 70 cancer patients matched for age and sex showed a statistically significant difference. Spontaneous elevated MN cell rates of cancer patients refer to previous exposition of genotoxic or mutagenic environmental agents. Moreover, the MN cell rates in cancer patients most probably refers to various cellular lesions and genetic damages.

The prognosis of pediatric neuroblastoma depends both on clinical presentation and on certain cellular and molecular characteristics. At the present time, two hypotheses can be drawn to explain both clinical and biological heterogeneity. In the first hypothesis, neuroblastoma progresses from early to late clinical stages through a classical multistep process linked to an accumulation of molecular abnormalities. In the second hypothesis, neuroblastoma represents an heterogeneous group of unrelated diseases, where most of stages I and II or stage IVS neuroblastomas can rather be considered as benign tumors, and stage IV neuroblastoma as a true malignant proliferation. To ascertain relevant biological factors for the prognosis of the disease, it is uppermost important that all investigators agree on biological criteria for analysis when neuroblastoma tissue is available in screened and unscreened populations. This paper reviews the biological tools available for prognosis in neuroblastoma, the priority for analysis of biological markers according to reliability, feasibility, and reproducibility of analysis procedure, and the conditions of tissue storage for further analysis of these biological markers. The standardized biological evaluation of neuroblastoma will allow, first, to collect sufficient data for multivariate analysis of prognostic factors and, second, to better define the putative links between various forms of the disease.

The treatment of cancer with alkylating drugs or topoisomerase II inhibitors can be responsible for the development of myelodysplastic syndromes and acute myelogenous leukemia. Alkylating agents such as melphalan and cisplatinum mainly produce damages at chromosomes 5 and 7 whereas topoisomerase II inhibitors-induced lesions essentially affect chromosomes 11 and 21. Rearrangements of the MLL gene at band 11q23 are frequently observed in human de novo myeloid and lymphoid leukemia as well as in leukemia or myelodysplasia secondary to therapy with drugs targetting topoisomerase II such as the epipodophyllotoxins. A relationship between the treatment with etoposide on teniposide and the development of translocations of the MLL gene has been clearly evidenced. The potential molecular basis of the chromosomal rearrangements implicating topoisomerase II and its inhibitors are discussed. The chemical structure of the inhibitors, their mechanism of action and the genes targetted by these drugs are presented. DNA cleavages induced directly by topoisomerase II inhibitors or by the drug induced apoptotic cellular response are responsible for nonrandom chromosomal aberrations and contribute to leukemogenesis.

This paper presents a sociological perspective of the experience of the cancer patient. Cancer is considered in the wider context of chronic and/or long-term illness which are typical of modern societies. The sociological concepts of "biographical disruption", "illness trajectory", "endless work and care" of the patient and his family are useful for analysing the experience of illness, and doctor-patient relationships. Moreover, they might illuminate some aspects of the individual and collective impact of modern oncogenetic technologies.

Ethical guidelines are necessary to help practitioners to deal with matters about which they are uncertainty and to solve problems where conflicting interests are at stake. To avoid doing harm is the first criterion to be adopted, in line with primum non nocere, as doing good is not enough (saving lives is not sufficient and one also has to consider whether a loss of dignity or suffering will not make the benefit worthless). Consultees must come to consultations freely and intentionally and must have control over the choices subsequently made. But others interests may be involved and ethical misconducts can arise in situations such as the following: family pressure about DNA testing, medical pressure to help other patients of for scientific purposes (sometimes merely to obtain data for publication). Geneticians must look at the reality underlying each situation, although complete autonomy and neutrality may be impossible to achieve. Individuals' rights are by now recognised, but the pursuit of autonomy at all costs has led to the development of a kind of self service medicine. One extreme situation of this kind was the request for prophylactic mastectomy made by a mutation free woman from a high risk family. Since this woman had seen her mothers and sister(s) die from breast cancer, her appraisal of her own risk may not fitted the neutrally calculated cumulative lifetime risk, which is about 9% (the so-called sporadic risk). Practitioners perceive contradictory elements during their consultations, and they ask for help. They cannot solve this kind of situation by themselves even by consulting the available medical, statistical and scientific knowledge. Other specialists (humanities) have to be consulted and asked to avoid wrong counselling.

Oncogenetics is a new discipline expanding very rapidly and depending on advances in understanding genes associated with inherited susceptibility to common adult malignancies. This discipline is still between a research field and a clinical service. This is very specific regarding medical management and services related to cancer genetic testing, directions for use genetic testing. It is the emergence of a so-called "predictive" medicine and in general of problems surrounding genetic testing for adult-onset disorders susceptibility. In the past years significant and unprecedented media fanfare informed both medical professionals and the general public. The opinions have moved from enthusiasm to skepticism but now a fair approach should be obtained. A good example of current controversies is breast cancer susceptibility. At the present time the oncogenetics debate "yes ... but on condition that ..." replace the previous one "in favour or against". The remained relevant topics are "how far" and "what for". Specific guidelines are already published or are on-going development. All of them point out a critical need for assessment (long-term outcome studies, multidisciplinary team approach for medical management, patient oriented research to analyse the psychological and social impact of genetic testing).

The on-going development of predictive tests for common cancers--as breast and colorectal cancers--is potentially introducing fundamental changes in medical practices, and, therefore, changes in the role and meaning of medicine in society. In this context, analysing the conditions of emergence and development of cancergenetics activities, and their potential implications, appears as an issue of particular interest for sociology. The study conducted at Inserm unit 379 in Marseille, in collaboration with physicians from institut Paoli-Calmettes, led us, firstly, to identify a set of factors as decisive for the future of these activities. In addition, this analysis highlights the diversity of the conditions of introduction of genetic tests, depending on the pathologies and the context of existing clinical practices. Considering these elements, we argue for the setting of adequate modalities of regulation so as to permit a managed and responsible introduction of genetic testing in medicine and society.

Interaction between developmental biology and human pathology has brought new insight on basal cell carcinoma oncogenesis. Alterations of the Patched gene appear to be responsible for the Gorlin syndrome and to be detected in 50% of the sporadic basal cell carcinomas. This relation has recently been extended to all the components of the Hedgehog signalling pathway.

The p16INK4a gene located in the MTS1 (multiple tumor suppressor 1) locus encodes two proteins, p16INK4a and p19ARF, which are structurally unrelated but functionally similar as both inhibit cell cycle progression. In this review, we report and comment new data obtained from mice knockouted for p19ARF without interfering with the expression of p16INK4a. This results in the rapid occurrence of a spectrum of tumors. These data establish that p19ARF is a genuine tumor suppressor protein and raise the questions of the relationship between the two proteins and their respective importance in malignancies.

Acute promyelocytic leukemia (APL) originate from chromosomal translocations generating two types of fusion proteins both involving the retinoic acid receptor alpha (RAR alpha) and either the gene PML (t(15;17)) or PLZF (t(11;17)). Recent publications cast a new light on the detailed molecular mechanism underlying the oncogenic activity of these fusion proteins which block myeloid terminal differentiation by recruiting histone deacetylases to the promoters of target genes through co-repressor proteins. They also explain the different responses to treatment by all-trans retinoic acid (ATRA) of these two variants which are otherwise clinically indistinguishable.

The purpose of the oncogenetic consultation, is to respond to persons who wonder about their risk of developing a tumour and wish to learn about ways of prevention and detection. The object of this investigation is (1) to study the impact of a first consultation in genetics on the quality of life and the psychology of women with a family history of cancer, and women with or without family antecedents but who suffered themselves from breast cancer at an early age (< or = 35 years); (2) to evaluate their risk perception and their comprehension of the information after the consultation. The study was performed on 200 women attending a first consultation at Institut Curie. Fifty-nine of them had no cancer. Among the 141 consultants with cancer, 54 had developed breast cancer at an early age (< or = 35 years). Their quality of life, their psychological state and their knowledge of the risk of breast tumour were evaluated before consulting and 6-8 months afterwards. Before consulting, their quality of life was altered in some (non-relational) fields but their psychic condition was relatively maintained. Six-nine months after consulting, their quality of life had not deteriorated, but tests results on their psychological state were not as good. The initial psychic condition, itself related to the medical status of the consulting women, was the most significant predictor of their quality of life a few months after their first genetics consultation. After consulting, the women expressed satisfaction with the information delivered by the genetician and their appreciation of tumour risks was improved.

Loss of chromosomes is a recurrent event in cancer. Chromosome-10 losses occur with tumor progression and characterize advanced gliomas. This chromosome carries many genes involved in glucose metabolism. Hexokinase (HK) gene is located on chromosome-10. Hexokinase enzymatic activity is decreased in glioblastomas. Hexokinase enables glucose entry into glycolysis and is critical for these highly glycolytic tumors. These enzyme is either free in the cytosol or bound to the mitochondrial outer membrane. Disturbance of HK binding to mitochondria by lonidamine led to inhibition of cells and xenografted-glioma growth. Hexokinase bind to a mitochondrial porin which involved peripheral benzodiazepine receptors. Inhibition of HK and peripheral benzodiazepine receptors by lonidamine and diazepam led to synergistic antitumoral activity in xenografted gliomas. Co-inhibition of these two receptors will lead to a decrease in glycolysis, often elevated in these tumors, without modifying energetic metabolism of normal cells.