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P. Merel

Bio: P. Merel is an academic researcher from Curie Institute. The author has contributed to research in topics: Neurofibromatosis type 2 & Point mutation. The author has an hindex of 10, co-authored 14 publications receiving 2203 citations.

Papers
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Journal ArticleDOI
10 Jun 1993-Nature
TL;DR: The 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.
Abstract: 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.

1,279 citations

Journal ArticleDOI
TL;DR: Results provide strong evidence that the suppressor gene on chromosome 22, frequently inactivated in meningioma, is the NF2 gene, and suggest that another gene is involved in the development of 40% of meningo-central nervous system tumours.
Abstract: Meningiomas are common central nervous system tumours which present usually in the 4th and 5th decades of life. Loss of constitutional heterozygosity on chromosome 22 in 60% of sporadic meningiomas has implied the involvement of a tumour suppressor gene. The neurofibromatosis type 2 gene (NF2), a prime candidate for involvement in meningioma, was screened for point mutations. After examining eight of the 16 known NF2 exons in 151 meningiomas, 24 inactivating mutations were characterized. Significantly, these aberrations were exclusively detected in tumours which lost the other chromosome 22 allele. These results provide strong evidence that the suppressor gene on chromosome 22, frequently inactivated in meningioma, is the NF2 gene, and suggest that another gene is involved in the development of 40% of meningiomas.

492 citations

Journal ArticleDOI
TL;DR: 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.
Abstract: 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. (C) 1995 Wiley-Liss, Inc.

129 citations

Journal ArticleDOI
TL;DR: A screening method for the detection of point mutations in NF2 which takes advantage of denaturing gradient gel electrophoresis (DGGE) and efficiently screens 95% of the coding sequence and 90% of intron/exon junctions.
Abstract: 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.

124 citations

Journal ArticleDOI
TL;DR: It is concluded that ependymomas resemble the other glial neoplasms with respect to type and location of the chromosomal changes involved and should be considered genetically as low‐grade gliomas.
Abstract: Ependymomas are glial cell-derived tumors. They are, in contrast to other gliomas (astrocytomas, oligodendrogliomas, and oligoastrocytomas), ill-defined with respect to the genes and chromosomal segments important in their tumorigenesis. In this study, we extensively screened I7 ependymomas for genetic changes characteristic of other gliomas. Allelic loss was detected on chromosome arm 22q in three tumors; on chromosome 10 in two tumors; on chromosome arm 17p in two tumors; and on chromosome arms 6q, 9p, I 3q, and I9q, each in one tumor. No allelic losses were found on chromosome arms I p and I6q. None of the tumors had EGFR gene amplification. In each case, the chromosomal segment affected by the deletion included the region known t o harbor a tumor suppressor gene important in glioma tumorigenesis. We conclude that ependymomas resemble the other glial neoplasms with respect to type and location of the chromosomal changes involved. Given the relatively infrequent occurrence of these genetic changes, ependymomas should be considered genetically as low-grade gliomas. © 1995 Wiley-Liss, Inc.

73 citations


Cited by
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TL;DR: Cell-adhesion molecules, once believed to function primarily in tethering cells to extracellular ligands, are now recognized as having broader functions in cellular signalling cascades and the CD44 transmembrane glycoprotein family adds new aspects to these roles by participating in signal-transduction processes.
Abstract: Cell-adhesion molecules, once believed to function primarily in tethering cells to extracellular ligands, are now recognized as having broader functions in cellular signalling cascades. The CD44 transmembrane glycoprotein family adds new aspects to these roles by participating in signal-transduction processes — not only by establishing specific transmembrane complexes, but also by organizing signalling cascades through association with the actin cytoskeleton. CD44 and its associated partner proteins monitor changes in the extracellular matrix that influence cell growth, survival and differentiation.

2,171 citations

Journal ArticleDOI
TL;DR: Recent studies suggest that the core Hippo kinase cascade integrates multiple upstream inputs, enabling dynamic regulation of tissue homeostasis in animal development and physiology.

2,008 citations

Journal ArticleDOI
05 Nov 2015-Cell
TL;DR: The Hippo pathway regulates cell proliferation, apoptosis, and stemness in response to a wide range of extracellular and intracellular signals, including cell-cell contact, cell polarity, mechanical cues, ligands of G-protein-coupled receptors, and cellular energy status.

1,571 citations

Journal ArticleDOI
31 Dec 1993-Cell
TL;DR: Northern blot analysis identified a shortened transcript, while reduced expression was observed in another TSC family, confirming TSC2 as the chromosome 16 TSC gene, and its protein product, tuberin, has a region of homology to the GTPase-activating protein GAP3.

1,513 citations

Journal ArticleDOI
TL;DR: The ezrin–radixin–moesin (ERM) proteins are crucial components that provide a regulated linkage between membrane proteins and the cortical cytoskeleton, and also participate in signal-transduction pathways.
Abstract: A fundamental property of many plasma-membrane proteins is their association with the underlying cytoskeleton to determine cell shape, and to participate in adhesion, motility and other plasma-membrane processes, including endocytosis and exocytosis. The ezrin–radixin–moesin (ERM) proteins are crucial components that provide a regulated linkage between membrane proteins and the cortical cytoskeleton, and also participate in signal-transduction pathways. The closely related tumour suppressor merlin shares many properties with ERM proteins, yet also provides a distinct and essential function.

1,347 citations