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Y J Bignon

Publications and source records attributed to Y J Bignon.

At least 55 records · Page 3Linked to original sources
PubMed1998

Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations.

BACKGROUND: We have previously demonstrated that breast cancers associated with inherited BRCA1 and BRCA2 gene mutations differ from each other in their histopathologic appearances and that each of these types differs from breast cancers in patients unselected for family history (i.e., sporadic cancers). We have now conducted a more detailed examination of cytologic and architectural features of these tumors. METHODS: Specimens of tumor tissue (5-microm-thick sections) were examined independently by two pathologists, who were unaware of the case or control subject status, for the presence of cell mitosis, lymphocytic infiltration, continuous pushing margins, and solid sheets of cancer cells; cell nuclei, cell nucleoli, cell necrosis, and cell borders were also evaluated. The resulting data were combined with previously available information on tumor type and tumor grade and further evaluated by multifactorial analysis. All statistical tests are two-sided. RESULTS: Cancers associated with BRCA1 mutations exhibited higher mitotic counts (P = .001), a greater proportion of the tumor with a continuous pushing margin (P<.0001), and more lymphocytic infiltration (P = .002) than sporadic (i.e., control) cancers. Cancers associated with BRCA2 mutations exhibited a higher score for tubule formation (fewer tubules) (P = .0002), a higher proportion of the tumor perimeter with a continuous pushing margin (P<.0001), and a lower mitotic count (P = .003) than control cancers. CONCLUSIONS: Our study has identified key features of the histologic phenotypes of breast cancers in carriers of mutant BRCA1 and BRCA2 genes. This information may improve the classification of breast cancers in individuals with a family history of the disease and may ultimately aid in the clinical management of patients.

Adult↗
PubMed1998

Seventh International Workshop on Ataxia-Telangiectasia.

Ataxia-telangiectasia (A-T) is a rare hereditary syndrome involving cerebellar degeneration, immunodeficiency, cancer risk, and radiosensitivity. Since the cloning of the A-T gene, ATM, in 1995, research on this pleiotropic disease and its molecular basis has expanded tremendously. ATM is a large protein kinase that appears to be one of the primary sensors of DNA strand-break damage. The vast majority of mutations in ATM result in truncation and destabilization of the protein, but certain missense and splicing errors have been shown to result in a less severe phenotype. A-T heterozygotes have been shown to have a slightly increased risk of cancer, but their increased in vitro radiosensitivity does not seem to result in any in vivo sensitivity. ATM does seem to act as a classic tumor suppressor gene in T-prolymphocytic leukemia, and LOH at the ATM locus is a common event in some tumor types, suggesting a general role for ATM in cancer. Recent work has shown the interaction of ATM with proteins involved in cell cycle control, and the direct phosphorylation of some of these interactors by ATM. ATM knockout mice have been created by several groups, and recapitulate the immunodeficiency, radiosensitivity, cancer risk, and fertility defects of A-T, although the effect on the cerebellum is slight. These diverse topics, and their integration into a global understanding of A-T, were the basis of the 7th International A-T Workshop.

Animals↗
PubMed1998

Allelic deletion at glutathione S-transferase M1 locus and its association with breast cancer susceptibility.

Glutathione S-transferases (GSTs) are a family of isoenzymes involved in cellular detoxification. Previous studies have correlated the absence of the GSTM1 protein with an increased risk of developing some cancers, especially lung or bladder cancer, in heavy smokers. In this study, we determined GSTM1 gene polymorphisms in a French western population of 437 female controls and 361 community breast cancer patients. Three distinct alleles of this gene may be identified: GST M1* A allele, GST M1* B allele, and GST M1* 0 allele (which is deleted). Null patients (GSTM1 0) are homozygous for the deletion. We determined in our two populations, patients with no, one or two GSTM1 alleles. The comparative analysis of our two populations did not demonstrate any statistically significant difference in GSTM1 allelotype distribution between the two groups (P = 0.43), although the null genotype was the more frequent in patients. The predominance of the null genotype was significant in the oldest group of patients (> or = 55) (P = 0.006), suggesting that GSTM1 null genotype may play an important role in breast cancer susceptibility in the elderly. This was not observed in the youngest age group, i.e. < 40 year old patients (P = 0.25), or in the patients aged from 40 to 55 years old (P = 0.37). Our results also point out a putative protective role of the A allele in the older female control group (P = 0.02), especially in subjects hemizygous for these alleles (P = 0.03). A prospective study will be of interest to investigate the effect of dosage of the gene.

Adult↗
PubMed1998

Consortium study on 1280 breast carcinomas: allelic loss on chromosome 17 targets subregions associated with family history and clinical parameters.

The pattern of loss of heterozygosity (LOH) on chromosome 17 in human breast cancer is complicated and shows many different regions of loss. In an attempt to narrow down the relevant regions of LOH on chromosome 17, we have studied the deletion pattern and its association with clinical parameters in 1280 breast carcinoma-venous blood lymphocyte pairs. In total, 42 different chromosome 17 loci were investigated, and between 25 and 625 cases were analyzed at each locus. The frequency of LOH observed on the p arm was much higher than that observed on the q arm. The opposite effect was observed in 52 ovarian cancer cases investigated, with less LOH on 17p than on 17q. Patterns of loss consistent with interstitial and terminal deletions, as well as loss of either the p or q arm or monosomy 17 were observed. To determine whether loss at particular loci may be associated with biological features of breast tumors, clinical data including age of onset, family history of breast cancer, tumor histopathology, tumor size, estrogen receptor (ER) status, and occurrence of lymph node or distant metastases were collected for each case. Overall, large-sized, ER-negative, lymph node-positive ductal tumors showed the highest frequencies of LOH, with ER-negative and ductal tumors showing LOH for markers along the majority of the chromosome. Eight regions of chromosome 17 appear to be associated with human breast cancer, two on 17p and six on 17q. These regions were not necessarily in the areas exhibiting the highest frequencies of LOH but were defined by interstitial and terminal deletions in multiple independent cases. Seven of these regions showed statistically significant differences in LOH associated with clinical parameters. These data strongly suggest that loci on chromosome 17 may determine aspects of tumor presentation and disease behavior in human breast cancer and pinpoint candidate tumor suppressor gene loci.

Adult↗
PubMed1998

Identification of recurrent and novel mutations in the LDL receptor gene in Spanish patients with familial hypercholesterolemia. Mutations in brief no. 135. Online.

We used the single strand conformation polymorphism (SSCP) method to investigate 13 apparently unrelated Spanish patients with familial hypercholesterolemia (FH) for mutations in the promoter region and the 18 exons and their flanking intron sequences of the low density lipoprotein (LDL) receptor gene. We found 16 aberrant SSCP patterns, and the underlying mutations were characterized by DNA sequencing. Five novel missense mutations, Q71E, C74G, C95R, C281Y and D679E, and one nonsense mutation, Q133X, were identified. We also found six missense mutations, S156L, D200Y, D200G, E256K, T413K and C646Y, and one stop codon mutation, W(-18)X, that were previously described in patients from other populations. A new frameshift mutation, 2085del19, was found in one patient. We also identified three splicing mutations; two of them are novel mutations, 1706-10G->A and 2390-1G->A, and the other one has been reported recently, 313+1G->C. Four patients were found to carry two different mutations in the same allele: Q71E and 313+1G->C; C95R and D679E; W(-18)X and E256K, and C281Y and 1706-10G->A. Our results demonstrate that there is a broad spectrum of mutations in the LDL receptor gene in the Spanish population.

DNA Mutational Analysis↗
PubMed1998

New mechanism of BRCA-1 mutation by deletion/insertion at the same nucleotide position in three unrelated French breast/ovarian cancer families.

A novel complex mutation consisting of a small deletion/insertion (3958del5ins4) was found in the breast cancer-1 gene (BRCA-1) in three unrelated French breast and/or ovarian cancer families. These mutations occurred at the same nucleotide position of the 3' end of exon 11. The wild-type sequence, CTCAG, was deleted and replaced by AGGC in the three families. The consequence is the generation of a stop codon, TAG, resulting in a truncated protein. We propose two different mechanisms to explain the generation of this complex mutation: (i) the simultaneous occurrence of a deletion and an insertion in a stem-loop structure and (ii) the abortive integration of a human transposable element (Tigger 1) that deleted 5 nucleotides and inserted a 4-nucleotide "scar", corresponding to the 5' extremity of the transposon.

BRCA1 Protein↗
PubMed1998

Cancer genetic clinics: why do women who already have cancer attend?

Cancer patients attend oncogenetic clinics so that the existence of a genetic risk can be checked and the relatives informed. The aim of this study was to describe the expectations of cancer patients about genetic counselling and their beliefs about the aetiology of their disease. A survey based on self-administered questionnaires before and after the consultation was carried out on 115 women with breast/ovarian cancer who attended one of the six French participating clinics. In 59 cases (51%), the consultees' expectations focused on the preventive options available and in 86 cases (75%) on their offspring; 87 (76%) found the consultation informative. On average, the women rated heredity and diet as lower risk factors (P < 0.05) after the consultation than before. Heredity, stress and the environment were thought to be more decisive than diet, smoking and alcohol. 34 patients who seemed unlikely to have a genetic risk in the consultant's opinion thought heredity to be less relevant (P < 0.05) after the consultation than before. At the time of the survey, cancer patients accounted for at least half of the consultees attending oncogenetic clinics in France. They need to have the clinical specificities of their disease and its medical management explained. They attend mainly for their offspring's sake, whereas healthy clients attend for their own sake.

Attitude to Health↗
PubMed1998

No evidence for constitutional ATM mutation in breast/gastric cancer families.

Ataxia-Telangiectasia (A-T) is a rare autosomal recessive disease characterised by cutaneous telangiectasia, cerebellar ataxia, immunodeficiency, high sensitivity to ionising radiation, chromosomal instability and an increased risk of cancer. The gene mutated in A-T patients, ATM, is located on chromosome 11q22-23. ATM heterozygotes are thought to have a high tendency to develop malignancies, such as breast cancer. In order to determine the contribution of heterozygous ATM mutation to cancer, studies of cancer-affected patients have been undertaken in non site-specific cancer families and sporadic breast cancer cases. No evidence of an important role of ATM heterozygous mutations has been shown. In order to give another contribution to these results, we tried to define a specific family phenotype according to the most common cancers observed in ATM heterozygotes. Breast and gastric cancers appear to be the most frequent malignancies in A-T carriers and one ATM germ-line mutation has been described in a breast/gastric cancer family. Therefore we further investigated the role of ATM mutation in additional breast/gastric cancer families. In eighteen families associating these two malignancies, we used the protein transcription/translation test to detect ATM mutations in the index case from each family. We found one case of ATM mutation which did not cosegregate with the gastric cancer in the family.

Adult↗
PubMed1998

Loss of heterozygosity of BRCA1, BRCA2 and ATM genes in sporadic invasive ductal breast carcinoma.

The present study was undertaken to analyse the loss of heterozygosity (LOH) of the three genes, BRCA1, BRCA2 and ATM, and their correlation to clinicopathological parameters in sporadic breast cancer. We studied 59 sets of invasive ductal carcinoma, compared to matched normal control DNA. Microsatellite markers intragenic to BRCA1 (D17S1323, D17S1322, D17S855), BRCA2 (D13S1699, D13S1701, D13S1695) and ATM (D11S2179) were simultaneously used. In addition, one marker telomeric to BRCA2 (D13S1694) and four markers flanking ATM were analysed (D11S1816, D11S1819, D11S1294, D11S1818). Thirty-one per cent of the informative cases showed loss of heterozygosity for the BRCA1 gene, 22.8% for BRCA2 gene and 40% for ATM. LOH of BRCA1 correlated with high grade tumors (p=0.0005) and negative hormone receptors (p=0.01). LOH of ATM correlated with higher grade (p=0.03) and a younger age at diagnosis (p=0.03) in our set of tumors. No correlations were detected between BRCA2 LOH and any of the analysed clinicopathological parameters. However, a correlation was detected between allelic loss of the D13S1694 marker, telomeric to BRCA2, and larger tumor sizes and negative estrogen receptors, favoring the hypothesis of the presence of another putative tumor suppressor gene, telomeric to BRCA2, in the 13q12-q14 region. Only 11 tumors had LOH at more than one of the three genes, most of them (6/11) associated LOH of BRCA1 and ATM. One tumor only combined loss of the three genes BRCA1, BRCA2 and ATM.

Adult↗
PubMed1998

[Cutaneous pseudolymphoma caused by carbamazepine].

INTRODUCTION: Drug-induced cutaneous pseudolymphomas are poorly reported. They clinically and pathologically mimic malignant lymphomas but their evolution is benign after drug withdrawal. CASE REPORT: We herein reported a case of carbamazepine++-induced pseudolymphoma in a 30 year-old woman of particular interest because of the paucity of clinical symptoms (only six papules of less than one centimetre each). COMMENTS: Phenytoins, carbamazepine++, barbiturates and ACE inhibitors are the main drugs inducing cutaneous pseudolymphomas. These usually mimic T-cell lymphomas. The clinical spectrum of cutaneous pseudolymphomas is broad including severe aspects, such as erythroderma or tumoral eruption and benign appearing one as in our case. Drug investigation is mandatory for each patient with lymphoma appearing cutaneous infiltrates because dramatic and definitive healing of the lesion is always expected in case of pseudolymphoma.

Adult↗
PubMed1998

[Search for microdeletions in the long arm of chromosome Y in 48 infertile men].

About 30% of infertilities are from male origin. They appear in some cases de novo and considered idiopathic. The aim of our work is to evaluate, in these cases, the Y chromosome long arm microdeletion prevalence within the AZF a, b and c regions by molecular biology technics. Were excluded from our study, azoo-oligospermia from hereditary, endocrine, obstructive origins or with a constitutional cytogenetic abnormality. 48 infertile men with a spermogram-proven azoo-oligospermia were studied. Among them, 30 were idiopathics, 8 out of them exhibited a genital infection past history or biological abnormalities suggesting partial obtruction of the genito-urinary tractus. 8 cases of varicocela and 10 of cryptorchidia were also studied. Peripheral blood DNA was extracted from each patient, then amplified by multiplex PCR with STS genomic markers from the 3 Y chromosome AZF zones. PCR products were then analysed on agarose gels. Considering the difficulty to affirm the absence of a signal in molecular biology, each suspicion of deletion was checked by multiplex PCR complication with the SRY marker. 5 Y chromosome long arm microdeletions were diagnosed among our 48 patients. All of them included the AZFc zone and the intragenic DAZ gene markers. Moreover a larger Y chromosome deletion encompassing the 3 AZF zones was diagnosed, and confirmed by the cytogenetic analysis. All the Y chromosome microdeletions were observed in the 22 truly idiopathic azoo/oligospermia, corresponding to a proportion of 22.7% which falls to 10.4% considering the whole population of 48 studied people (closer to the published data). The relatively high proportion of microdeletions found in our series, underlines the need of a strict patient selection to avoid unnecessary search for long arm Y chromosome microdeletions.

Chromosome Deletion↗
PubMed1997

[Epidemiology and genetics of cancers of the ovary].

5% of ovarian cancers occur in a hereditary predisposition context. Clinical syndromes are defined by 3 or more cases of breast or ovarian cancers, or cancers from the Lynch-type II spectrum (colon, endometrium...) in one family branch. When the diagnosis is established, genetic counselling is provided to the kindred, a molecular diagnosis is undertaken for BRCA1 and BRCA2 genes, screening for ovarian and other at risk cancers is proposed, or prophylactic oophorectomy is proposed for at least 35 years old women without children conception projects.

Causality↗