Recent technical advances in immunology and molecular genetics have allowed to better delineate Ewing sarcoma among other small round cell tumors of bone and soft tissues. Ewing cells present with a characteristic translocation t (11;22) (q23-24; q11-12) shared with neuroepithelioma. They express a series of cell-surface antigens associated with the neuroectodermal differentiation lineage. These data open new avenues for exploring the origin and the mechanism of transformation of these tumors and to conceive new therapeutical approaches.

Cytogenetic studies performed on 130 consecutive childhood acute non lymphoblastic leukemias (ANLL) and investigated in the same center between 1977 and 1986 have been studied for their prognostic value. Clonal chromosome changes were detected in 68.5% (89/130) of the cases prior to treatment. Complete remission rate and median survival were significantly lower in patients with only abnormal metaphases than in patients with only normal metaphases (NN) or a mixture of normal and abnormal mitoses (AN). The ANLL with translocation t(8;21), which were 58.6% of the M2 ANLL, were not associated with a particularly long survival (16 months) when compared with AN and NN ANLL. The longest survival (26 months) was observed in patients with acute myelomonocytic leukemia with bone marrow eosinophilia. Cytogenetic analysis have a prognostic value in childhood ANLL.

To test the large number of hypotheses proposed as causes for childhood leukemia, a case control study was carried out on every child diagnosed for acute leukemia between 1.1.1977 and 12.31.1982, under the age of 15 and living in the region of Lyon (Rhône-Alpes and Saône-et-Loire). Some factors could not be confirmed, possibly in relation with the relatively small sample size (208 cases). Others were confirmed, especially the excess of incidence among 2 to 4 year old children and those belonging to higher socioeconomic groups. Two new factors were identified: the age of the father (over 40 years at child birth) and the profession of the father (manipulation of meat in the few years prior the diagnosis of leukemia in the child).

Three cases of M5 acute leukemia, 1 with a t(8;16)(p11;p13), 2 with variant translocations, both with a breakpoint at band 8p11, t(6;8)(q27;p11) and t(8;19)(p11;q13) are reported and 12 other published cases reviewed. This is a rare new entity, of variable but rather poor prognosis, seen from birth to 75 years of age, with several cases in infants. Leukemic cells, which often show conspicuous phagocytic activity on bone marrow smears, bear both monocytic and granulocytic markers in at least some cases. The best therapeutic regimen is not well-defined. The molecular basis of the disorder remains to be elucidated.

T and B cells specifically recognize antigens using a receptor located at the cell surface. The repertoire of lymphoid cells chiefly results from somatic rearrangements involving the variable segments of the genes encoding these receptors. The modifications of the DNA structure induced by these rearrangements are found in all cells of the same clone. Immunoglobulin (Ig) or T-cell antigen receptor (TCR) gene rearrangements are usually found in most lymphomas as well as in B or T lineage acute lymphoblastic leukemias. Thus, the study of Ig or TCR gene rearrangement could be useful in the detection of minimal disease in such malignancies. However the sensitivity of molecular hybridization on Southern blots is still not a sensible enough technique to be used in clinical practice.

Autologous bone marrow transplantation is now a major tool in the treatment of human leukemias and lymphomas. Evaluation of residual disease by standard cytological methods is difficult. Cytogenetics provide clonal markers which are specific features of leukemic cells. Detection of minimal disease by chromosomal methods is possible in acute leukemias, it requires karyotyping of a few hundred metaphases from a short term culture. A preselection of the material to be examined will improve the degree of sensitivity of the method.

Six patients of the same family present with micronodular and generalized familial angiomatosis. Four of them have been investigated. Their problem is purely esthetic; however an asymptomatic form of von Willebrand disease has been found in a female and one of her daughters. The light microscope reveals a network of dilated capillaries in the superficial dermis. Electron microscope investigation of the endothelium demonstrates on abundance of Weibel-Palade bodies, the presence of osmiophilic inclusions within clear vacuoles, the occurrence of long spacing collagen fibrils in the vicinity of endothelial and perithelial cells; furthermore, cytoplasmic projections within the lumen constitute the most dramatic and constant feature: there are many villosities, loops, coils, tufts and entanglements in all four cases.

The authors report three cases of benign tumours of the occipito-cervical skeleton, remarkable for their rarity and especially by their unusual, even exceptional anatomic site: an osteoid osteoma, a pre-medullary chondroma and an extra-dural exostosis developing within a hereditary multiple disease. This presentation which allows to recall a few epidemiological and diagnostic problems is essentially focused on operative strategy and particularly on the choice of the best way to cope with surgical difficulties to be met. The osteoid osteoma whose diagnosis is difficult raises two surgical problems: the relation with the vertebral artery and the preservation of the atlanto-occipital joint. An approach through limited occipital craniotomy has allowed a perfect control of the vertebral artery and a complete removal without joint damage. Pre-medullary chondroma: a complete removal has been performed through the anterior way as described in rare observations of the literature. Post operatively, the patient had a complete neuro-orthopedic recovery. The antero-lateral exostosis has been removed through the posterior way by first resecting the basis of implantation, which has allowed the mobilization of the lesion without cord damage. Results have been good in the three cases both from neurological and orthopedic points of view.

Cytogenetic data are now available in most bone and soft tissue sarcomas. The characteristic chromosomal rearrangements observed are of great importance for the diagnosis, the classification and the comprehension of these cancers at the molecular level.

Activation of cellular proto-oncogenes can be detected in several human cancers. In neuroblastoma, amplification and overexpression of N-myc oncogene have been shown to be associated with advanced stages of disease and rapid tumor progression. These results suggest the clinical importance of the N-myc oncogene. Other oncogenes might also be activated in this cancer.

Expression of the gene encoding the nuclear phosphoprotein p53 (a proto-oncogene classified in the same functional family as c-myc and E1a adenovirus gene) was examined in a human T-cell leukemia (KE-37R cell line). No p53 (or a modified product) could be detected by immunoprecipitation with monoclonal antibodies P Ab 421 and P Ab 122 in KE-37R cell extracts, and no p53-specific RNA was characterized by Northern blot analysis. Southern blot using a murine p53 cDNA clone as a probe, did not reveal any gross rearrangement in the structure of the gene. However, this molecular probe was not suited for investigating the 5' end of the gene which contains the promoter and the non coding exon 1. It is interesting to notice that in KE-37R cells, c-myc has been activated by a t(8; 14) (q24; q11) translocation, suggesting that the c-myc product might substitute to some functions normally requiring p53.

Oncogenes are genes for malignant transformation which correspond to changes, by genetic mutation, of genes which are present in all normal eukaryotic cells, called proto-oncogenes. The latter are involved in physiological functions often controlling growth and cell differentiation. Their mechanism of action and the activation of oncogenes are successively anticipated. These oncogenes are implicated in the majority of cancers and in particular in bronchial carcinoma: the myc-oncogenes (c-myc, N myc, L myc) are primarily activated in small cell carcinomas (CPC), the Ras genes (Ki Ras, Ha Ras) in epidermoid and adeno carcinomas. The intervention of growth factors such as bombesin in CPC and of their receptors such as epithelial growth factor (EGF) in non small cell bronchial carcinomas has been shown, as well as the role of cytogenic abnormalities (deletion of the short arm of chromosome 3). Their relation to oncogenes is discussed. The knowledge acquired on oncogenes in bronchial carcinoma should shed light on the pathogenesis of these cancers and find its next application in the diagnostic, prognostic and therapeutic field.

A brief description of the results obtained by cytogenetic analyses of cancer cells from colorectal adenocarcinomas is reported. Two distinct patterns of chromosomal anomalies are observed. The major one, called "monosomic type", because many chromosomes losses exist, is characterised by the losses or deletions of the following chromosomes 18, 17 (short arm = p), 1p, 4, 14, 5 (long arm = q) and 21. It frequently evolves towards polyploidy, by duplication of all remaining chromosomes. The minor one, called "trisomic type", is characterised by the gain of several chromosomes: 7, 12, X, 5 and 8. The chromosomal anomalies observed seem to have no topological relationships with oncogenes, and other interpretations for their occurrence were investigated. The numerous and frequent deletions of some chromosomes, like 17p and 18, may indicate the involvement of recessive genes, like in the anti-oncogene system. In addition, it is observed that most deletions involve genes for "de novo" pathways whereas gains involve genes for salvage pathways of the synthesis of nucleotides. A correlated cytogenetic and enzymologic study was thus developed, and the first results show that the chromosomal pattern may well indicate the metabolic deviations. Monosomic type tumors have, on the average, a relatively low "de novo" and a high salvage pathways, and trisomic type tumors a high "de novo" and salvage pathways. Since chemotherapy is principally orientated against "de novo" pathways of the synthesis of nucleotides, these results may help to understand the difficulties of chemotherapy in colorectal cancers and perhaps to adapt it better.

Two new cases of Cowden's disease observed in two young sisters are reported. The diagnosis was based on the clinical observation of oral mucosa lesions (gingival hyperplasia, papillomatosis, scrotal tongue). In one case, visceral manifestations in childhood were observed. Cowden's disease is a familial affection (autosomal dominant trait) characterized by association of oral mucosa and skin lesions and of multiple hamartomas involving glandular tissues. Clinical and familial history investigations are justified by the high risk of malignant tumors (breast carcinoma).

Isolated communities offer a unique opportunity for the study of biological and social consequences of consanguinity and migration. The studies of genetic polymorphisms have contributed greatly, not only to knowledge of the genetic constitution of a given individual and population, but also to clarify either relationship between structure and function of polymorphic traits or the susceptibility to multifactorial diseases, in which interaction between the gene and environment cannot be ignored. For over 25 years, we have investigated the effect of consanguinity and genetic polymorphisms in 9 isolated communities in Western Japan. We reported here different values of gene frequency for each polymorphic trait, compared with the neighboring communities and described how we applied these data to clarification of the genetic constitution of isolated communities as well as of genetic susceptibility to some diseases.

The c-myb gene was studied in 112 breast cancers. c-myb and estrogen receptor (ER) transcripts were found in 78 (70%) and 71 (63%) cancers respectively. Of these 71 ER positive cancers, 64 (90%) contained c-myb transcripts and of the 41 ER negative cancers, 27 (66%) did not contain c-myb mRNA. Our data show that c-myb transcripts are strongly associated with ER and progesterone receptors (p less than 10(-4) status in breast cancer. Thus the c-myb expression could be associated with breast cancers of better prognosis and its analysis could allow a better characterization of new subsets of hormono-dependent cancers responding more efficiently to hormonotherapy.