Histoprognostic grade in tumours from families with hereditary predisposition to breast cancer.
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Adult↗
Biomedical subjects
Y J Bignon
Publications and source records attributed to Y J Bignon.
Lack of germ-line mutations in the p53 gene exons 4 to 8 in patients with late-onset second malignant neoplasms.
Previous studies have shown p53 germ-line mutations in some familial cancer aggregations with or without the Li-Fraumeni syndrome (LFS). Such mutations were also reported in children and young adults with second malignant neoplasms (SMN). This led us to screen for p53 germ-line mutations in a group of seven patients affected with SMN, but characterized by an older age of onset than in the previous reports. No mutation was found in exons 4 to 8 and their boundaries using the single-strand conformation polymorphism technique. Our results give strong evidence for genetic heterogeneity of SMN, probably related to the age of cancer onset.
Adult↗
[Criteria of genetic predisposition to hereditary non polyposis colorectal cancers].
Clinical and histological characteristics of non polypoid colorectal cancers with an hereditary predisposition are presented. The various known genetic syndromes (hereditary non polyposis colorectal cancers, Lynch syndrome type I and type II, Torre-Muir's syndrome, hereditary flat adenoma syndrome) are discussed to find a possible correlation between this nosological classification and their molecular substratum. The main problem today, is to correctly define the population of hereditary predisposed patients to colon cancer, in order to seek and identify the major responsible gene. Any physician, specialist or not, should be encouraged to give the details of the cancer familial context of his patients, in order to aid the oncologist geneticist in his task.
Adult↗
[Genetics and cancer of the breast].
Breast carcinoma is the commonest cancer in women. Segregation analyses support the existence of a major susceptibility gene with a dominant pattern of inheritance in 4 to 10% of cases. Three genes involved in the genetic predisposition to breast tumors have recently been identified: BRCA-1 associated with early onset familial breast cancer and breast/ovarian carcinoma syndrome, p53 associated with Li-Fraumeni syndrome, and the androgen receptor gene in male breast cancer with Reinfenstein syndrome. A better understanding of inherited contribution may have important implications for screening individuals at high-risk in families.
Ataxia Telangiectasia↗
Detection of allelic losses on 17q12-q21 chromosomal region in benign lesions and malignant tumors occurring in a familial context.
A predisposing gene (BRCA-1) for breast and ovarian cancer has been located on chromosomal region 17q12-21. According to Knudson's hypothesis if this gene is a tumor suppressor gene, allelic losses would be found in tumors occurring in families with cancer aggregations. We studied 25 samples of both benign lesions and malignant tumors, from breast cancer site-specific families and other familial cancer aggregations. Allelic losses seem to be more frequent in tumors from breast site-specific families but also include the predisposing locus in other syndromes, suggesting a role of BRCA-1 in such families. Finding of allele losses near this locus in benign lesions suggests that such alterations may represent a first step in breast carcinogenesis. It is noteworthy that allele losses involve larger chromosome fragments in malignant tumors than in benign lesions where BRCA-1 is not lost, suggesting a similar mechanism for genomic deletion in the tumorigenesis of the colon and of the breast.
Alleles↗
Screening of inherited breast cancer with DNA markers.
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Adult↗
Expression of a retinoblastoma transgene results in dwarf mice.
Introduction of the normal retinoblastoma gene (RB) into different tumor cells possessing inactivated RB genes suppresses their tumorigenicity in nude mice. These results suggest that RB replacement is a potential strategy for developing future clinical treatments of cancer. In a transgenic mouse model, we found that the quantity of RB protein in a given cell may play an important role in dictating its effect. Four founder mice containing 1-7 copies of a human RB cDNA transgene under the transcriptional control of the human RB promoter were generated. Most of the transgenic mice were smaller than nontransgenic littermates. This effect was found as early as embryonic day 15. The degree of dwarfism correlated roughly with the copy number of the transgene and the corresponding level of RB protein. The expression pattern of the transgene products was similar to that of the endogenous mouse RB gene with regard to tissue and temporal distribution. Transferring the transgene to RB deficient mice, which are nonviable, resulted in the development of normal, healthy mice, indicating that the human RB gene can functionally complement the mouse homolog. These studies demonstrate that the effect of RB on overall mouse development is closely dependent upon its dosage.
3T3 Cells↗
Linkage analysis of 19 French breast cancer families, with five chromosome 17q markers.
Nineteen French breast and breast-ovarian cancer families were tested for linkage with five chromosome 17q markers. The five breast-ovarian cancer families as a group give positive evidence for linkage, whereas the 14 breast cancer-only families do not. Heterogeneity of linkage of breast and breast-ovarian cancers is significant in France and supports the existence of more than one susceptibility gene.
Adult↗
Familial ovarian carcinoma: pedigree studies and preliminary results from linkage analysis.
Thirty-seven ovarian cancer-prone families have been identified through a French co-operative network. Three main clinical presentations were observed: site-specific ovarian cancer, breast/ovarian carcinoma syndrome and Lynch syndrome II. An additional kindred with features of Li-Fraumeni syndrome is reported. It is expected that a better understanding of the mechanisms of carcinogenesis will allow the development of new methods of screening and treatment. With this aim, recent studies have mapped the gene for early-onset familial breast cancer and breast/ovarian carcinoma syndrome to the same locus in the chromosome 17q12-q23 region. Results from linkage analysis of two breast/ovarian carcinoma families and three breast cancer families favour the hypothesis of genetic heterogeneity among breast and ovarian tumors.
Adult↗
[Hereditary predisposition for cancer of the breast and the ovary].
Familial breast cancers represent about 10% of all cases of breast cancers. A predisposition locus has been located in the 17q21 chromosomal region. Nineteen French breast and breast-ovarian cancer families were tested for linkage with five highly polymorphic 17q markers. The five breast-ovarian cancer families as a group give positive evidence for linkage, whereas the 14 breast cancer families do not. Heterogeneity of linkage of familial breast cancer is significant in France and supports the existence of more than one susceptibility gene.
Adult↗
[The retinoblastoma gene: will therapeutic use of its tumor suppressive properties be possible?].
The retinoblastoma is a rare childhood tumor which occurs in children, 40% of them being diagnosed in an hereditary context. The gene involved in the hereditary predisposition and in the tumoral development was isolated (RB-1) and is of the antioncogene-type. RB-1 mutations were found in many other tumors. The absence of the antioncogene protein expression is responsible for the tumor development and a contrario its presence in normal cells has tumor suppressive properties. This property was demonstrated by phenotype reversion of retinoblastoma or other cell lines (with no RB-1 protein), induced by reintroduction of the gene coding for the normal RB-1 protein. The normal RB-1 protein undergoes multiple phosphorylations during the cell cycle, regulating its activity, the active form being hypophosphorylated. RB-1 is involved in the transcription regulation of many cell cycle genes, and in cell differentiation. Experimental animal models are under investigation, in order to established whether RB-1 overexpression in normal cells will protect them from tumor development, and to plan tumor gene therapy by injection of recombinant viruses allowing RB-1 expression in tumor cells.
Child↗
Neoadjuvant chemotherapy in 126 operable breast cancers.
126 patients with non-inflammatory operable breast cancer, who otherwise would have undergone modified radical mastectomy (MRM), were treated by induction chemotherapy. Before treatment, every patient had a local and general assessment, and pathological or cytological evidence of malignancy. Patients received, every 3 weeks, the same treatment with doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil (AVCF); methotrexate was added in 80 cases (AVCFM). Tumour shrinkage greater than 50% was documented in 105 (83%) of the 126 women. A higher objective response rate was obtained in aneuploid or high S phase tumours, especially in the patients treated with methotrexate. After chemotherapy, 41 patients were then treated by radiotherapy alone after complete or sub-complete response; 64 had a residual tumour that could be treated by conservative surgery and radiotherapy. Only 19 had MRM and radiotherapy. Histopathological complete remission was documented in 1 case; isolated residual tumour cells were found in 5 patients. Thus primary chemotherapy enhanced the possibility of breast conservation in up to 83% of the cases in a series in which most would have been otherwise subjected to a MRM because of tumour size.
Adjuvants, Pharmaceutic↗
Effect of epidermal growth factor in HLA class I and class II transcription and protein expression in human breast adenocarcinoma cell lines.
The spontaneous expression of HLA class I and class II molecules in two human breast carcinoma cell lines (MCF7, T47D) and their modulation during epidermal growth factor treatment are reported. Transcription was analysed by Northern blot and hybridisation with HLA class II and class I cDNA specific probes. The expression of cell surface determinants was examined by internal protein labelling with 35s-methionine, immunoprecipitation with monoclonal antibodies specific for HLA class I or class II, followed by isolation of the immune complex on protein A-Sepharose; at least a quantification of glycoprotein was performed by chromatofocusing. Glycoprotein quantification showed a significant increase of HLA class I and class II (DR) antigen expression after stimulation by epidermal growth factor (0.02 microgram ml-1) in the two cell lines, when compared with untreated cell controls. However, with epidermal growth factor treatment of MCF7 and T47D cells, low increases in the amounts of HLA class I and class II RNA were obtained. These differences between expressed antigens and correspondent RNA amounts would be explained by the fact that EGF in these two cell lines acts more in post-transcription for HLA class I and class II antigens.
Adenocarcinoma↗
Hydantoin-induced cutaneous pseudolymphoma with clinical, pathologic, and immunologic aspects of Sézary syndrome.
BACKGROUND: The phenytoin-induced hypersensitivity syndrome is characterized by the development of fever, rash, lymphadenopathy, and hepatitis associated with leukocytosis and eosinophilia. This article describes the unusual occurrence of a pseudo-Sézary syndrome in the days following the introduction of phenytoin treatment. OBSERVATION: A phenytoin-induced erythroderma developed in a 60-year-old woman the histologic, cytologic, and immunologic characteristics of an erythrodermal cutaneous T-cell lymphoma of the Sézary syndrome type with lymph node involvement. The dramatic improvement after withdrawal of drug therapy and the absence of recurrence 5 years after led us to consider it as a hydantoin-induced pseudolymphoma. CONCLUSIONS: Although lymph node pseudolymphomas induced by phenytoin are well known, few cases of hydantoin-induced mycosis fungoides have been reported in the literature. We present herein the first case of a Sézary-like syndrome associated with phenytoin therapy. Such a patient must be monitored regularly because of the risk of a true malignant lymphoma developing even many years later.
Aged↗
Genotypic analyses of Richter's syndrome.
The authors report the immunogenotype of two cases of Richter's syndrome. The immunoglobulin gene rearrangement pattern obtained on Southern Blot analysis was found in both cases to be the same in leukemic blood cells and in the tissue involved by the lymphoma. The beta chain and gamma chain T-cell receptor gene rearrangement pattern exhibited a germ-line configuration in the peripheral blood cells and in the lymph node in Case 2, whereas in Case 1 the lymph node had a gene rearrangement in the beta chain, as well as in the gamma chain T-cell receptor, and the leukemic cells from bone marrow were found to be in a germ-line configuration for T-cell receptors (beta and gamma chains).
Aged↗
Detection of Epstein-Barr virus sequences in primary brain lymphoma without immunodeficiency.
We searched for Epstein-Barr virus (EBV) sequences by enzymatic DNA amplification in nine primary brain lymphomas from patients without immunodeficiency. We used seven nonlymphoma brain tumors as negative controls, and the Raji cell line as a positive control. We detected EBV DNA, using ethidium bromide-stained-agarose minigel electrophoresis and dot blot hybridization, in the positive control and in only one brain lymphoma tumor; we did not detect EBV DNA in the other tumors. The EBV-positive patient had a second B-cell monoclonal population in the peripheral blood without detectable EBV DNA, suggesting a direct role for EBV in the development of the brain lymphoma.
Brain Neoplasms↗
Clonotypic heterogeneity in cutaneous T-cell lymphomas.
The antigen receptor genes studied (immunoglobulin gene for B-cells, and T-cell receptor -beta or -gamma gene for T-cells) represent the most powerful tools for diagnosing the clonality of a lymphoid lineage. We have clonotyped 23 cutaneous T-cell lymphomas and 5 were found to be clonotypically all heterogeneous. Analysis of each patient was performed either from serial skin biopsies taken several months apart or from different tumor samples. In these cases, T-cell lymphoma clonotypic heterogeneity was demonstrated and was especially evident when examining different tumor sites. Moreover, in one case, a biogenotypic population (immunoglobulin and T-cell receptor-rearranged) was found. This unexpected high frequency of T-cell clonal heterogeneity (22%) could be explained either by the evolution of subclones from a single undifferentiated malignant cell or by the independent transformation to cancer of 2 or more lymphocytes, though the latter seems less likely. Clonotypic heterogeneity seems to be as frequent in T-cell lymphomas with cutaneous lesions as in B-cell leukemias.
Gene Rearrangement↗
[Adjuvant medical treatment].
Adjuvant medical treatments (chemotherapy or endocrine therapy) are now used in the vast majority of women with breast cancer. They delay recurrences and reduce their number, the increase in survival being particularly marked in limited forms. They also reinforce local treatment and increase the possibility of breast conservation. Their indications can be better determined by precise analysis of prognostic factors, notably tumoral cells.
Adjuvants, Pharmaceutic↗