The etiology of breast cancer is a complex interplay of various factors, including genetic alterations. A number of studies have been made to identify and characterize mutations that frequently occur during breast tumorigenesis. In this paper, we have described a new deletion, located on the long arm of chromosome 7. Patients whose tumor carried a deletion on chromosome 7q had a significantly shorter survival time. These findings identify the long arm of chromosome 7 as a candidate region for a putative tumor (or metastasis) suppressor gene.

Ataxia telangiectasia (AT) is a hereditary disease transmitted in a recessive mode and characterized by chromosomal instability and radiosensitivity. AT patients have a 100-fold higher risk of cancer than the general population. Although AT is a rare disease of which the frequency has been estimated to be 1/40,000, the frequency of the heterozygosity status, when assessed with the Hardy-Weinberg equation is high (about 1.4%). Parents of AT children, thus obligate AT carriers, show chromosomal instability and radiosensitivity, but at a lower level than AT patients. Assuming that these AT characteristics deal with the cancer predisposition, it can be hypothesized that AT heterozygote individuals have a higher cancer susceptibility than the general population. To test this hypothesis, M Swift's group compared cancer incidence rates from adult blood relatives of AT patients with controls. The risk of cancer in AT heterozygotes could be increased by 3.5 and, for carrier women, the breast cancer risk could be increased by 5.1. Actually, the diagnosis of the AT heterozygote status is not possible. However, the near cloning of the gene (or genes) for the disease will permit to identify the AT carriers in a population of patients suffering from cancer and to assess precisely the impact of AT heterozygosity in the genetic predisposition to cancer.

The HuIFN-alpha and beta genes were examined by the PCR method in the 11 human lymphoblastoid cell lines. The results showed that the homozygous deletion of HuIFN-alpha and beta genes was detected in 5 of 11 cell lines and in 5 of 11 cell lines, respectively. The deletions of both the HuIFN-alpha and beta genes were observed in 4 of 11 cell lines. One T cell leukemia cell line deleted only HuIFN-alpha gene, while the other T cell leukemia line deleted only HuIFN-beta gene. This suggests that the deletions of HuIFN-alpha and beta genes may be related the development of leukemia or lymphoma.

Most chromosome aberrations in gliomas are numerical, resulting in either gains or deficiencies of whole chromosomes. In tumors of low malignancy, the karyotype is frequently normal or exhibits a loss of sex chromosome and a gain of chromosome 7. These two anomalies may not be directly related to malignancy. In the highly malignant cases, the two most frequent aberrations are the gain of chromosome 7 and the loss of chromosome 10, other anomalies such as losses or deletions of chromosomes, 9, 22, 6, 13 and 14 being detected at various frequencies. Several of these chromosomes carry important genes of adenine metabolism: AK1 and AK3 (adenylate kinase) and MTAP (methylthioadenosine phosphorylase) for chromosome 9; ADK (adenosine kinase) and mitochondrial ATPase for chromosome 10; ADSL (adenylosuccinate lyase) for chromosome 22, NP (nucleoside phosphorylase) for chromosome 14. We performed the corresponding assays of enzyme activity on both fresh tumors and tumors grafted on nude mice, which showed that these enzymes had a relatively low activity although the tumors were proliferating. However, chromosome losses do not seem to directly cause the metabolic alterations by gene dosage effect. Interestingly, chromosome 10, frequently deficient, also carries genes of importance for glycolysis (hexokinase) and glutamate metabolism (glutamate dehydrogenase and glutamate oxaloacetate transaminase). The deficiency for these genes could be taken into account for a better type of chemotherapy by antimetabolics.

In human breast carcinoma MCF-7 cells, phorbol diesters inhibit proliferation and induce cell maturation. We investigated the involvement of TGF-beta 1 in the PCK-mediated inhibition of breast cancer cell proliferation. Using an RNase protection assay, we showed that TPA induced a dose-dependent increase in levels of TGF-beta 1 mRNA that paralleled the inhibitory effect on MCF-7 proliferation. Similar results were obtained with another TPA-sensitive breast cancer cell line (BT-20). TPA did not increase TGF-beta 1 mRNA levels in the MCF-7:RPh-4 and T47D cell lines, which are both insensitive to the growth inhibitory effects of phorbol esters. In addition, the increase in TGF-beta 1 mRNA level was not observed after treatment of the MCF-7 cell with other inducers of cell differentiation such as forskolin, DMF, HMBA and sodium butyrate. The induction of TGF-beta 1 mRNA by TPA along with its inhibitory effect on cell proliferation suggests that TGF-beta 1 mediates, at least in part, the inhibitory effect of PKC activation.

Cytology is an old method of diagnosis: it is the microscopical observation of cells in the aim of their identification, of the recognition of morphological abnormalities to obtain diagnosis or prognosis informations. During the last 20 years, new technics have been developed: 1) Immunocytochemistry permits the identification of the tissue or the organ of which a tumoral cell population is born, the determination of its stage of differentiation, its kinetic and the diagnosis of bone marrow or lymph node metastasis. 2) With in situ molecular biology, it becomes possible to detect, at the cell level, virus, oncogenes or chromosomic abnormalities. 3) Flow and image cytometry are easy means for DNA content determination and for an objective and reproducible cell definition. None of these methods are able, at this time, to replace the cytological analysis, but they are useful, sometimes necessary, for the diagnosis and the prognosis evaluation of malignancy.

Basic fibroblast growth factor (bFGF or FGF-2) is present in the basal membrane of pancreatic cells during the pancreatic embryonic development. The expression of bFGF receptors has been described in normal pancreatic cells. By contrast, pancreatic cancer cells express not only the bFGF receptors but also the bFGF itself. With the aim of understanding the effects induced by the production of bFGF by pancreatic cancer cells, the pancreatic acinar cell line (AR4-2J) was used. AR4-2J cells do not produce bFGF but express bFGF receptors. These cells were transfected with a vector containing the bFGF cDNA encoding the three different forms of bFGF characterized in tumor cells. Results showed that the bFGF expression induced important phenotypic and enzymatic modifications. The transfected cells lost some morphological features of the acinar cells and expressed amylase and lipase at low levels (a 90% decrease for amylase activity, whereas lipase activity was barely detectable). These results suggest that bFGF could be involved in maintaining pancreatic cells in a slightly differentiated state.

After a review of the literature concerning oncogenes expression of in head and neck carcinomas, the authors studied RAN extraction, in vitro transduction and two dimensional analysis of oncoproteins in head and neck carcinomas. The results between the tumoral tissue and normal tissue were compared significantly more oncoproteins spots were found in the tumoral tissue analysis.

The authors report one case of Drash syndrome: association of Wilms' tumor, nephropathy and genital abnormalities. The definition, prognosis and origin of this triad are discussed.

The anaplastic large cell, CD30 positive lymphomas represent a heterogeneous group of lymphomas in which immunocytochemical and molecular investigations have demonstrated the existence of malignancies of T, B or undetermined origin. The recent identification, in a few cases of this group of a chromosomal 5q35 breakpoint may allow the individualization of a peculiar disease entity. In these cases, the 5q35bp has been found to be a permanent abnormality, present in five human permanent cell lines and associated with various translocations including t(2;5), t(1;5) and t(5;6). A primitive myelo-monocytic origin of these 5q35bp cell is suggested on the basis of the following arguments: they express the c-fms proto-oncogene which encodes the macrophage growth receptor (CSF-1-R) the c-fms is mapped on 5q33,34 close to the 5q35bp the express spontaneously CD68 the treatment by phorbol-diester of a 5q35bp cell line (DEL cell line) induces an immunodependent phagocytosis and a modulation of expression of c-fms, CSF-1 and TNF alpha. Because some 5q35bp cell lines also presents rearrangements for TCR-bêta, or IgF, these data suggest an ancestral stem cell origin, prior to the T, B and myelomonocytic differentiation. Whatever its origin, the 5q35bp abnormality has been mainly encountered in children's malignancies. It has been constantly associated with clinical and biological manifestations of a condition recognized by paediatricians as malignant histiocytosis. For this reason, the 5q35bp may today represent the best criterion for the identification of malignant histiocytosis in childhood.

Gardner's syndrome ie an autosomal dominant disease characterized by the association of a polyposis coli with one or more of specific extracolonic manifestations. A lebanese family is reported. Polyposis coli, desmoid tumors, gastroduodenal polyps, procreation counselling etc. are difficult problems to manage in this syndrome.

Three cases of parathyroid neoplasms in familial hyperparathyroidism are reported. There were not associated with other endocrine glands or parathyroid glands lesions. Parathyroid gland carcinoma was diagnosed in 2 cases. Review of 7 cases of familial parathyroid carcinoma, diagnosed in 5 different families and issued from the literature, indicates that it can be associated to multiple endocrine neoplasia or other parathyroid lesions. The familial parathyroid carcinoma entity needs further studies before to be fully recognised.

Acute leukemia in the newborn child is a rare event. The clinical and biological characteristics differ from those normally encountered in the older child. Tumoral syndrome and extra-medullar locations are frequently described in the literature. Many authors have noted the difficulty of diagnosis due to the immaturity of the malignant proliferation. While it is generally agreed that therapeutic abstention is justified in the leukemoid reaction in Down's syndrome, the choice is debatable in the phenotypically intact newborn. For this reason, blastic karyotype analysis is essential and may provide guidelines when considering treatment. We report on a case history of acute monoblastic leukemia with translocation 9;11 that was diagnosed at birth in a normal newborn infant. The juxtaposition of c-ets 1 protooncogene and the beta-interferon gene has been associated with this kind of cytogenetic disease and probably constitutes a model for human leukemogenesis.

Vitamin A (retinol) and retinoic acid, its natural derivative, play an important role in the growth, differentiation and development of known normal tissues. Retinoids have recently become of interest to research in areas as diverse as dermatology, embryonal development and cancer research. Retinol is the major retinoid transported in the blood and tissues by its specific carrier retinol binding protein (RBP). The normal level of retinol in plasma is regulated very precisely by retinol homeostasis. RBP-retinol circulation supplies target cells, which then activate retinol into retinoic acid (RA) if they possess the NAD-dependent enzymatic oxidation system. RA, which is one of the most active metabolites of retinol, is also present in low concentration in the blood and the RA rate formation varies from tissues depending on specific need of the cell. The cellular transport and biological activity of retinoids may be mediated by their specific cytoplasmic binding proteins cellular retinol binding protein (CRBP) and the cellular retinoic acid binding protein (CRABP) which may function as shuttles targetting RA to nucleosol fraction and/or as regulator of cellular concentration of RA. The nuclear proteins RARs (retinoic acid receptors), which are members of the nuclear receptor superfamily are likely to be the final transducers of the RA signal at the gene expression. All-trans retinoic acid (ATRA) is able to specifically differentiate the malignant cells from leukemic patients with APL in short-term culture. For this reason, APL patients were successfully treated with ATRA (Chinese and French results). Acute promyelocytic leukemia M3 (French-American-British FAB classification) is a rare disease (10% of AML), characterized by a reciprocal chromosome 15-17 translocation. It has been shown that the chromosome 17 breakpoint of the translocation is localized within the RAR alpha gene. Due to the t(15;17) RAR alpha gene translocated to a gene PML on chromosome 15 resulting in synthesis of PML/RAR alpha fusion messenger RNA. Detection of PML/RAR alpha transcript is now a molecular marker of the disease. The abnormal PML/RAR alpha protein exhibits altered transcription activation properties when compared with RAR alpha. Clinical trials have demonstrated that ATRA is extremely efficient in inducing complete remission in APL patients. The morphologic finding of maturing elements in the bone marrow and peripheral blood during retinoic acid treatment indicates that the remission is obtained without hypoplasia and suggests that a differentiating mechanism is involved.(ABSTRACT TRUNCATED AT 400 WORDS)