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Biomedical subjects

M Sanson

Publications and source records attributed to M Sanson.

At least 55 records · Page 3Linked to original sources
PubMed1996

[Biology and gene therapy of glioma].

Although prognosis of malignant gliomas did not change dramatically for the last 15 years, tumorigenesis is much better understood. The study of the genetic alterations occurring in these tumors allowed to recognise the most critical genes involved, which are either overexpressed oncogene, or inactivated tumor suppressor gene. Gene therapy is a natural outcome of such progresses. One way of tumor gene therapy is based on correction of genetic defect either by introducing the missing tumor suppressor gene or by blocking overexpression of an activated oncogene. Alternatively, "destructive" gene therapy is based on a "suicide" gene introduced in tumor cells. These approach results now in phase 1 protocol.

Adult↗
PubMed1996

Treatment of recurrent malignant supratentorial gliomas with ifosfamide, carboplatin and etoposide: a phase II study.

Thirty-six patients previously treated with surgery, radiation therapy and chemotherapy with a nitrosourea for malignant supratentorial gliomas received a combination of ifosfamide, carboplatin and etoposide (ICE) at tumour progression. Carboplatin and etoposide were both given at a dose of 75-100 mg/m2/day for 3 days, whereas ifosfamide doses ranged from 750 mg/m2/day to 1500 mg/m2/ day for 3 days, according to haematological tolerance. Treatment was repeated every 4 weeks. A minimum of three courses was required to evaluate the response unless the patient had rapid tumour progression. Grade III and IV haematological toxicity occurred in 15 patients (42%) and was lethal in one patient. Grade II hepatic toxicity was observed in one patient. Five complete (CR) and five partial responses (PR) were noted. 9 patients had stable disease (SD) after a minimum of three courses. CR + PR + SD was 53% (19/36). The median time to tumour progression (MTTP) was 13 weeks. Median survival (MST) was 29 weeks (44 weeks for R + S patients and 17 weeks for patients with progressing disease). This study suggests that the ICE combination is active in recurrent supratentorial malignant gliomas after failure of surgery, radiation therapy and chemotherapy, but at the cost of substantial haematological toxicity.

Adult↗
PubMed1996

[A new tumor suppressor gene responsible for type 2 neurofibromatosis is inactivated in neurinoma and meningioma].

Neurofibromatosis type 2 (NF2) is an autosomal dominant disease which predisposes to multiple schwannomas, meningiomas and to a lesser extent, to ependymomas. These tumours have been shown to display frequent loss of chromosome 22. Gene defect causing NF2 has been mapped on chromosome 22. Using positional cloning, we and others recently isolated the gene responsible for NF2. Its product displays strong homology with membrane organizing protein suggesting that this protein, called either Schwannomin or Merlin, could act as a bridge between membrane and cytoskeleton. Alterations of the NF2 gene have been identified in NF2 patients and result usually in a truncated, presumably inactive protein. Analysis of tumoral DNA from sporadic schwannomas and meningiomas demonstrates complete loss of function in many cases, providing evidence that the NF2 gene acts as tumor suppressor gene. As a consequence, genetic presymptomatic diagnosis of at risk individuals for NF2 is now possible.

Genes, Neurofibromatosis 2↗
PubMed1995

Incidence of germ-line p53 mutations in patients with gliomas.

Epidemiological studies on intracranial tumors have suggested that the observed familial aggregation of a proportion of gliomas may be due to inherited predisposition to their development. In the Li-Fraumeni syndrome (LFS) associated with germ-line mutations of the p53 gene, nervous-system tumors are observed with increased frequency. However, the contribution of germ-line p53 mutation to the incidence of brain tumors has not been investigated. In order to address this point, we have performed 2 independent investigations. First, we have examined an unselected series of brain tumors. Whenever the presence of a p53 mutation in the tumor was observed, the possible germ-line origin of the mutation was investigated. Germ-line p53 mutations were also analyzed in constitutional DNA of patients with gliomas that had been selected for an unusual personal or familial history of cancer. Germ-line p53 mutations were detected in 1 out of 80 unselected cases and in 3 out of 15 selected cases (20%). We conclude that germ-line p53 mutation may contribute to a small fraction of gliomas that develop in the general population. The presence of a personal or familial history of cancer in a patient with glioma should prompt the search for a germ-line p53 mutation. However, the low frequency of p53 germ-line mutation suggests that alterations of this gene may not account for most familial cases of gliomas.

Amino Acid Sequence↗
PubMed1995

Screening for germ-line mutations in the NF2 gene.

Neurofibromatosis type 2 (NF2) is a monogenic dominantly inherited disease that predisposes to the development of tumors of the nervous system, particularly meningiomas and schwannomas. The gene which, when altered, causes NF2, is localized on chromosome 22 and has recently been identified. The NF2 gene is also the site of somatic mutation in tumors, suggesting that it might have a tumor suppressor activity. We here report a screening method for the detection of point mutations in NF2 which takes advantage of denaturing gradient gel electrophoresis (DGGE). This method efficiently screens 95% of the coding sequence and 90% of intron/exon junctions. When applied to 91 unrelated NF2 patients, it enabled the identification of 32 germ-line mutations. Since mutations are found in only one third of the patients, it is expected that mutations or deletions affecting the promoter and/or intronic regions of the NF2 gene occur frequently. The characterized mutations are preferentially located within the 5' half of the gene. Most of them are predicted to lead to the synthesis of a truncated protein. A search for genotype/phenotype correlations showed that, at least in this series of patients, mild manifestations of the disease were associated with mutations which preserve the C-terminal end of the protein.

Base Sequence↗
PubMed1995

Predominant occurrence of somatic mutations of the NF2 gene in meningiomas and schwannomas.

The NF2 gene is a putative tumor-suppressor gene that, when it is altered in the germline, causes neurofibromatosis type 2, a tumor-susceptibility disease that mainly predisposes to schwannomas and meningiomas. The recent isolation of the NF2 gene on chromosome 22 allows the identification of somatic mutations in human tumors. We have searched for mutations of the NF2 gene in 331 primary human tumors using a screening method based on denaturing gradient gel electrophoresis, which allows the detection of mutations in 95% of the coding sequence. Mutations were observed in 17 of 57 meningiomas and in 30 of 89 schwannomas. No mutations were observed for 17 ependymomas, 70 gliomas, 23 primary melanomas, 24 pheochromocytomas, 15 neuroblastomas, 6 medulloblastomas, 15 colon cancers, and 15 breast cancers. All meningiomas and one-half of the schwannomas with identified NF2 mutations demonstrated chromosome 22 allelic losses. We conclude that the involvement of the NF2 gene in human tumorigenesis may be restricted to schwannomas and meningiomas, where it is frequently inactivated by a two-hit process.

Brain Neoplasms↗
PubMed1995

The oculopharyngeal muscular dystrophy locus maps to the region of the cardiac alpha and beta myosin heavy chain genes on chromosome 14q11.2-q13.

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant muscular dystrophy which presents typically after the age of 50 with progressive eyelid drooping and an increasing difficulty in swallowing. Though OPMD has a world-wide incidence, it is more common in the French Canadian population. We have identified a homogeneous group of families and studied 166 polymorphic markers as part of a genome search before establishing linkage to chromosome 14. We determined that the OPMD locus maps to a less than 5 cM region of chromosome 14q11.2-q13. The maximum two-point lod score in three French Canadian families of 14.73 (theta = 0.03) was obtained for an intronic cardiac beta myosin heavy chain gene (MYH7) marker. The regional localization for the OPMD locus raises the intriguing possibility that either the cardiac alpha or beta myosin heavy chain genes may play a role in this disease.

Base Sequence↗
PubMed1995

[Peripheral neurological complications of Epstein-Barr virus infection].

Neurological complications associated with infectious mononucleosis, although well described, are rare. We report a patient with a meningo-radiculitis due to Epstein-Barr virus. A review of published literature on neurological manifestations associated with the Epstein-Barr virus is presented.

Adult↗
PubMed1994

The neurofibromatosis type 2 gene is inactivated in schwannomas.

Schwannomas are tumors arising from schwann cells surrounding peripheral nerves. Although most schwannomas are sporadic, they are seen in approximately 90% of individuals with neurofibromatosis type 2 (NF2), an autosomal dominantly inherited disease with an incidence of 1:40000 live births. The NF2 gene has recently been isolated on chromosome 22 and encodes a putative membrane organizing protein named schwannomin. It is believed to act as a tumor suppressor gene based on the high frequency of loss of heterozygosity (LOH) on this autosome in both sporadic and NF2 associated schwannomas and meningiomas and the identification of inactivating mutation in NF2 patients. In this study we examined 61 schwannomas including 48 sporadic schwannomas (46 of which are vestibular schwannomas) and 12 schwannomas obtained from NF2 patients, for mutations in 10 of the 16 coding exons of the NF2 gene. Twelve inactivating mutations were identified, 8 in sporadic tumours and 4 in tumors from people with NF2. These results support the hypothesis that loss of function of schwannomin is a frequent and fundamental event in the genesis of schwannomas.

Base Sequence↗
PubMed1994

[Primary meningeal gliomatosis].

A 44 year old woman presented with chronic meningitis. Magnetic resonance imagery showed a diffuse contrast enhancement of the leptomeninges. Cerebrospinal fluid studies showed a high hyperproteinorachia and light pleiocytosis. A left temporal tumor appeared four months later. Histological studies revealed an anaplastic oligosatrocytoma leading to the diagnosis of primary leptomeningeal gliomatosis.

Adult↗
PubMed1994

Molecular cytogenetic analysis of a series of 23 DiGeorge syndrome patients by fluorescence in situ hybridization.

The authors have studied a series of 23 DiGeorge syndrome patients by prometaphase chromosome analysis and/or by FISH with a set of 6 cosmid probes spanning the previously described commonly deleted region. Four patients display a cytogenetically visible interstitial deletion in band 22q11.2, whereas the other 18 patients exhibit a molecular deletion evidenced only by FISH analysis. For 21 of the patients studied, the deletion encompasses the 6 loci tested, while for one, only the most telomeric of these loci is conserved. The last patient does not show any deletion with the probes used.

Adolescent↗
PubMed1993

Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2.

Neurofibromatosis type 2 (NF2) is a monogenic dominantly inherited disease predisposing carriers to develop nervous system tumours. To identify the genetic defect, the region between two flanking polymorphic markers on chromosome 22 was cloned and several genes identified. One is the site of germ-line mutations in NF2 patients and of somatic mutations in NF2-related tumours. Its deduced product has homology with proteins at the plasma membrane and cytoskeleton interface, a previously unknown site of action of tumour suppressor genes in humans.

Amino Acid Sequence↗
PubMed1993

Isolation and mapping of 45 NotI linking clones to chromosome 22.

Fifty-nine NotI linking clones have been isolated from a flow-sorted chromosome 22 cosmid library and mapped using fluorescence in situ hybridization and/or a panel of somatic cell hybrids. Fourteen clones map to the short arm of chromosome 22, 31 to the long arm, and 9 to other chromosomes; 5 clones could not be unambiguously mapped. To identify potentially informative genetic markers, the chromosome 22 clones were screened for poly(CA) sequences; 24 positively hybridizing clones, 10 on the long arm and 14 on the short arm, were identified. These clones will be useful for constructing a long-range restriction map of chromosome 22 and may facilitate the cloning of chromosome 22 genes.

Base Sequence↗
PubMed1993

Germline deletion in a neurofibromatosis type 2 kindred inactivates the NF2 gene and a candidate meningioma locus.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disease which predisposes to the development of schwannomas, meningiomas, ependymomas, and juvenile cataracts. The NF2 gene (NF2) has recently been isolated and maps to chromosome 22q12 between the loci D22S212 and D22S32. Deletion studies in sporadic and NF2 associated schwannomas and meningiomas, and the presence of inactivating mutations in NF2 in patients suggest that it acts as a tumor suppressor gene. A candidate meningioma gene (MEN) has also been isolated from the same interval. A new highly polymorphic (CA)n marker, D22S268, which maps very near to NF2, has allowed us to identify a kindred with three living affected individuals, where the disease is presumably caused by a large germline deletion. Fluorescence in situ hybridization and pulsed field gel electrophoresis confirm the presence of a 700kb deletion which includes the neurofilament heavy chain subunit gene locus (NEFH), D22S268, NF2 and the putative MEN gene. The absence of meningiomas in this pedigree raises doubts as to the existence of a separate MEN locus in this region. These results support the hypothesis that NF2 results from the inactivation of a tumor suppressor gene on chromosome 22q.

Cells, Cultured↗