Retinoblastoma (RB) is the most frequent ocular tumor in childhood. Due to recent advances in molecular biology, RB has become a study model for cancer suppressor genes, and antenatal diagnosis has now become feasible. The goals of therapy include an improved survival rate, decrease in iatrogenic sequelae (especially enucleation), and avoidance of radio-induced neoplasias. This review examines recent data from the literature.

Considerable advances were made during the Eighties in the treatment of acute lymphoblastic leukemia in children, using an intensive treatment regimen. The impact of numerous diagnostic variables on the prognosis has been modified; their re-evaluation as prognosis factors is necessary. Great importance is now attributed to the appreciation of the tumor burden, to the immunophenotype, and most importantly to cytogenetic data. This paper describes the prognosis factors currently used to define risk-group, and risk-adapted treatment regimen.

Although epidemiologic studies have clearly demonstrated the importance of the hepatitis B virus in the genesis of hepatocellular carcinoma, the molecular basis for this tumorigenic effect is still under debate. The finding of hepatitis B virus DNA integration into human liver DNA in many cases of hepatocellular carcinoma suggested that these integrated viral sequences may be involved in liver carcinogenesis. In an attempt to clarify this point, we studied 9 tumors which developed in non cirrhotic livers. All tumors contained viral integrations (ranging from 1 to 6 different integrants) and 4 showed abnormal hepatitis B virus mRNA (2.3 to 7.5 kilobases long). The analysis of the corresponding cDNAs revealed the existence of hybrid transcripts containing both genomic and viral sequences. In 2 cases, the viral-host junctions were mapped within the cohesive-end region of the hepatitis B virus genome leading to the production of a transcript encoding a 3' truncated X protein. In another case, the cellular sequences present in the co-transcript were located in 5' with respect to the hepatitis B virus sequences. This observation strongly suggests that, in this patient, integration took place near a cellular gene. Further analysis of this integrant should help in identifying the putative gene and its application in the development of the tumor. We conclude that the study of abnormal hepatitis B virus transcripts in liver tumors provides a positive approach to study the direct role of HBV in carcinogenesis as an insertional mutagen.

In the last ten years considerable progress has been made in small-cell lung carcinoma (SCLC) biology, along with the technical progress made in molecular biology. This progress now allows us to propose a model for the genesis and the development of this type of tumor. Tobacco, the principal causal factor plays a dual role. In bringing about secretion of growth factors by the bronchial epithelia, usually involved in the normal development of lungs, and by functioning autocrinally and paracrinally, it facilitates the occurrence of mitotic mutations. Without directly contributing to cellular transformation, this autocrine functioning also gives a selective advantage to cells going through transformation or immortalization. The procarcinogenic or carcinogenic agents contained in tobacco smoke, whose level of production could be genetically determined, would also contribute to the accumulation of mutations affecting both suppressor genes and oncogenes. Two tumour suppressor genes have been identified: RB1 and P53. At least one other putative tumour suppressor gene has constantly been implied. It lies on the short arm of chromosome 3. There could also be the possibility of detecting subjects susceptible to developing an SCLC, a functional hemizygote still needing evaluation. The activated oncogenes principally belongs to the myc family. Their activation could correspond with the appearance of cellular clones having aggressive behavior independent of growth factors, chemoresistant and more metastatic. SCLC may be distinguished from other malignant lung tumors by a fairly characteristic pattern consisting of the loss of suppressor genes and the activation of oncogenes. The links between the neuroendocrine properties of this type of tumor and its characteristic description are being clarified and will contribute to a better understanding of the relationship between the different types of lung tumors. From this biologic knowledge follow several therapeutic applications under investigation (blocking autocrine loop through anti-GRP antibodies), as well as potential applications (concerning the products of suppressor genes) and possible applications such as prevention oriented towards detection of high-risk subjects.

The use of probes detecting polymorphic loci within the human population has enabled accurate localization of the genetic defect responsible for familial adenomatous polyposis on chromosome 5. This was used to screen two families for the presymptomatic diagnosis in children of an affected parent. In both cases, the use of 8 polymorphic probes located on either side of the gene provided information which could be used in the management of children born from the patients at risk. The set of probes used in this work should be informative in most of the affected adenomatous polyposis families.

There are now rather straightforward methods to create transgenic animals whose genome is altered at the germline level. One method consists in the micro-injection of a gene into the pronucleus of a fertilized egg, the second one involves an homologous recombination event obtained in embryonic stem cells in culture. Only the latter method could eventually lead to an authentic gene therapy since it could actually substitute a normal gene for a mutated one instead of merely introducing a supplementary gene as done by micro-injection. Description of these techniques makes it obvious that germline therapy of human beings would not only be inacceptable on ethical grounds but would also hardly have any medical indications. Quite on the contrary, somatic gene therapy does not suffer from the same reservations and has numerous potential applications to man. As a matter of fact, several protocols have already received approval and have reached the stage of clinical trials: for example SCID (severe combined immunodeficiency due to a mutated adenosine deaminase gene), AIDS as well as some forms of malignant tumors.

Genes, which are implicated in the pathogenesis of human tumors, may demonstrate Restriction Fragment Length Polymorphism (RFLP). Population studies of such RFLP are of potential interest for a genetic analysis of cancer susceptibility. The initial data of Krontiris et al has shown a significant increase of rare c-Ha-ras-1 alleles in individuals with tumors. Since then, other significant associations have been found between other genes RFLPs and various tumors. In this paper, we report that L-myc RFLP may prove useful in identifying breast cancer patients at high risk of developing lung metastases.

The etiology of cancer is a complex interplay of various factors, including genetic alterations. Multiple studies have been carried out to identify and characterize mutations that frequently occur during tumorigenesis. In human breast cancer, amplification of proto-oncogenes (c-myc, c-erbB-2/neu) and chromosome 11q13, mutation of p53 and loss of heterozygosity (chromosomes 1, 3p, 6q, 7q, 11p, 13q, 16q, 17, 18q and 22q) represent the major types of genetic abnormalities that have been frequently observed in tumor DNAs. The genetic deletions and mutations could inactivate tumor-suppressor genes. In some studies, specific alterations have been associated with some clinical parameters. Recently, linkage analyses, on large families with a predisposition to breast cancer, have been performed to map putative breast cancer susceptibility genes. The survey of high risk patients should be organised to make an earlier diagnosis.

Flow cytometry DNA analysis of fragments of fresh or paraffin-embedded tumor was performed in order to investigate its prognostic value in renal cell carcinoma. As aneuploidy is a frequent cytogenetic finding of these cancers, it is not surprising that the literature reports a high incidence of anomalies of DNA content, affecting 2/3 of cases studied. DNA aneuploidy is more frequent in advanced stages, high grades and spindle-cell carcinomas. Its prognostic value in terms of the survival of nephrectomized patients has been demonstrated by unifactorial studies. Several studies using Cox's model have demonstrated its independence of stage and grade, but they are too limited for DNA ploidy to be considered to be an element of the therapeutic decision. In contrast with other sites, the prognostic influence of the proliferation evaluated by S% does not appear to be as important as DNA ploidy. Prospective studies comparing these results should take into account the tumor heterogeneity observed in this type of cancer by analysing, for example, several fragments of the same tumor.

The aetiopathogenesis of adult renal tumors is poorly understood. The specific chromosomal changes detected by the study of tumor karyotypes suggest a cascade of oncogene activation and tumor suppressor gene inactivation in the course of renal carcinogenesis. These cytogenetic studies have isolated two entities: non-papillary carcinomas (clear cell and/or eosinophil carcinomas) and tubulopapillary tumors (cortical adenoma, basophil papillary carcinoma). Specific changes of the short arm of chromosome 3 are observed in 70 to 85% of cases of clear cell carcinomas, while trisomy 17 is detected in 70% of cases of tubulopapillary tumors. Cytogenetics is also able to distinguish low and high grade malignant tubulopapillary carcinomas. Limited data are available at the present time concerning oncocytomas.

Tubulopapillary tumors of the kidney represent a group of peculiar interest with specific histological and cytogenetic features. These tumors are distinguished from other renal tumors by their more favorable prognosis.

We report the case of 41 year-old male patient, in whom multiple and recurrent infrequent cutaneous lesions (sebaceous adenomas) led to suspect the diagnosis of Muir-Torre syndrome. This diagnosis was confirmed when 2 colo-rectal adenocarcinomas were discovered and curatively excised (trans-anal excision, followed by total colectomy). The Muir-Torre syndrome was part of a familial cancer syndrome in this case, as the patient's mother and brother died from colonic cancer before the age of 45. The case-report underlines the diagnostic role of cutaneous lesions in this syndrome, allowing early detection of internal malignancy.

The epidermal growth factor receptor gene is the most frequently involved proto-oncogene in human glial brain tumors, in the present series in agreement with previous reports in literature. It is therefore important to study this gene from DNA to the protein product. The vicinity of cystic fluid (C.F.) to tumor cells of the cystic wall has suggested investigation of possible "E.G.F.-like" autocrine activities in C.F. In 40% of gliomas, E.G.F.-R. gene is amplified and overexpressed. This is never observed in low grade astrocytomas. In 12% of the cases, mutations of the E.G.F.-R. gene are observed. In correlation with genomic abnormalities, E.G.F.-R. is immunoprecipitated in 40% gliomas. The basal phosphorylation of the receptor is increased in 50% gliomas. In C.F., unexpectedly, E.G.F.-R. phosphorylation inhibitory effect is observed. Its biochemical analysis suggests an anti-tyrosine kinase activity. The observation of anti-tyrosine kinase activity in C.Fs suggests the presence of negative modulatory factors of the proto-oncogene activation in tumor tissues. This could have therapeutical interest.

Over the last 24 years the authors operated 21 branchiomeric paragangliomas in 18 patients. They emphasize the difficulty of making the diagnosis and the importance of completing a thorough work-up before deciding surgery. Adequate imaging is particularly important (neck sonography, computed tomography, arteriography) to avoid making the diagnosis by exploratory neck dissection and to assess the vascular risk. Biological studies have regained importance, especially in the context of complex neuro-cristopathy. Treatment is essentially surgical and must be considered with prudence in patients with bilateral lesions. The surgical removal of branchiomeric paragangliomas necessitates preparation of a small saphenous vein bypass in case it is not possible to avoid sacrificing the internal carotid artery.

This paper describes the progressive changes in cancer incidence that have been observed among Japanese after their migration to Hawaii. It reviews descriptive and analytic epidemiologic data suggesting a role for genetic susceptibilities in explaining the high risk of Japanese for colon cancer and their low risk for lung cancer, when compared to Caucasians. Differences in certain pharmacogenetic polymorphisms may explain these risk patterns. This research may lead to a better characterization of cancer risk at the individual level and, consequently, to improved methods of prevention.