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NF2 (neurofibromatosis type 2)

Written1997-09Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated1998-03Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated2001-02James F Gusella
Molecular Neurogenetics Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA

(Note : for Links provided by Atlas : click)

Identity

Other aliasSCH
LocusID (NCBI) 4771
Atlas_Id 117
Location 22q12.2  [Link to chromosome band 22q12]
Location_base_pair Starts at and ends at bp from pter
Local_order 22q12.1-12.2 junction, incidentally not far from EWS
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CABP7 (22q12.2) / NF2 (22q12.2)EWSR1 (22q12.2) / NF2 (22q12.2)FBXO10 (9p13.2) / NF2 (22q12.2)
GSTT1 (-) / NF2 (22q12.2)NF2 (22q12.2) / CABP7 (22q12.2)NF2 (22q12.2) / CLTCL1 (22q11.21)
NF2 (22q12.2) / EIF3D (22q12.3)NF2 (22q12.2) / GRAP2 (22q13.1)NF2 (22q12.2) / HSD3B2 (1p12)
NF2 (22q12.2) / LSM14A (19q13.11)NF2 (22q12.2) / NF2 (22q12.2)NF2 (22q12.2) / PI4KA (22q11.21)
NF2 (22q12.2) / PIEZO2 (18p11.22)NF2 (22q12.2) / RHOT1 (17q11.2)NF2 (22q12.2) / TCF20 (22q13.2)
RHOT1 (17q11.2) / NF2 (22q12.2)TCF20 (22q13.2) / NF2 (22q12.2)

DNA/RNA

Description exons 17 exons (1-15, 17 constitutive, 16 alternatively spliced); spans 120 kb; open reading frame: 1.8 kb
Transcription alternate splicing, in particular after exon 15

Protein

Description called merlin, schwannomin, or SCH; isoform 1 595 amino acids, isoform 2 590 amino acids (due to inclusion of exon 16 in transcript) ; 66 KDa; NH2 -- FERM domain -- large a helix domain -- COOH
Expression wide: in lung, kidney, ovary, breast, placenta, neuroblasts; high in fetal brain
Localisation membrane associated interacts with integral membrane proteins and actin-cytoskeleton
Function membrane-cytoskeleton anchor (as APC also appears to be); role in the development of extraembryonic structures before gastrulation; has characteristics of a tumour suppressor, as has been found in sporadic as well as neurofibromatosis type 2 induced schwannomas and meningiomas
Homology ezrin, radixin, moesin, members of the erythrocytes band 4.1 family, especially in the N-terminal FERM domain

Mutations

Germinal inborn condition of neurofibromatosis type 2 patients: protein truncations due to various frameshift deletions or insertions or nonsense mutations; splice-site or missense mutations are also found; phenotype-genotype correlations are observed (i.e. that severe phenotype are found in cases with protein truncations rather than those with amino acid substitution)
Somatic mutation and allele loss events in tumours in neurofibromatosis type 2 and in sporadic schwannomas and meningiomas are in accordance with the two-hit model for neoplasia, as is found in retinoblastoma

Implicated in

Note
  
Entity neurofibromatosis type 2
Disease autosomal dominant tumor prone disease; neurofibromatosis type 2 (NF2: the same symbol is used for the disease neurofibromatosis type 2 and the gene) is an hamartoneoplastic syndrome
Prognosis hamartomas have a potential towards neoplasia; those, in NF2, are The tumors of NF2 are slow-growing benign schwannomas which do not progress to malignancy and meningiomas
  
  
Entity sporadic meningioma
  
  
Entity sporadic schwannoma
  
  
Entity other tumours: ependymoma; mesothelioma
  

Bibliography

Impaired interaction of naturally occurring mutant NF2 protein with actin-based cytoskeleton and membrane.
Deguen B, Mérel P, Goutebroze L, Giovannini M, Reggio H, Arpin M, Thomas G
Human molecular genetics. 1998 ; 7 (2) : 217-226.
PMID 9425229
 
Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2.
Giovannini M, Robanus-Maandag E, van der Valk M, Niwa-Kawakita M, Abramowski V, Goutebroze L, Woodruff JM, Berns A, Thomas G
Genes & development. 2000 ; 14 (13) : 1617-1630.
PMID 10887156
 
Merlin: the neurofibromatosis 2 tumor suppressor.
Gusella JF, Ramesh V, MacCollin M, Jacoby LB
Biochimica et biophysica acta. 1999 ; 1423 (2) : M29-M36.
PMID 10214350
 
The parental origin of new mutations in neurofibromatosis 2.
Kluwe L, Mautner V, Parry DM, Jacoby LB, Baser M, Gusella J, Davis K, Stavrou D, MacCollin M
Neurogenetics. 2000 ; 3 (1) : 17-24.
PMID 11085592
 
Advances in neurofibromatosis 2 (NF2): a workshop report.
Lim DJ, Rubenstein AE, Evans DG, Jacks T, Seizinger BG, Baser ME, Beebe D, Brackmann DE, Chiocca EA, Fehon RG, Giovannini M, Glazer R, Gusella JF, Gutmann DH, Korf B, Lieberman F, Martuza R, McClatchey AI, Parry DM, Pulst SM, Ramesh V, Ramsey WJ, Ratner N, Rutkowski JL, Ruttledge M, Weinstein DE
Journal of neurogenetics. 2000 ; 14 (2) : 63-106.
PMID 10992163
 
The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation.
McClatchey AI, Saotome I, Ramesh V, Gusella JF, Jacks T
Genes & development. 1997 ; 11 (10) : 1253-1265.
PMID 9171370
 
Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity.
Parry DM, Eldridge R, Kaiser-Kupfer MI, Bouzas EA, Pikus A, Patronas N
American journal of medical genetics. 1994 ; 52 (4) : 450-461.
PMID 7747758
 
Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease severity and retinal abnormalities.
Parry DM, MacCollin MM, Kaiser-Kupfer MI, Pulaski K, Nicholson HS, Bolesta M, Eldridge R, Gusella JF
American journal of human genetics. 1996 ; 59 (3) : 529-539.
PMID 8751853
 
Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2.
Rouleau GA, Merel P, Lutchman M, Sanson M, Zucman J, Marineau C, Hoang-Xuan K, Demczuk S, Desmaze C, Plougastel B
Nature. 1993 ; 363 (6429) : 515-521.
PMID 8379998
 
Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease.
Ruttledge MH, Andermann AA, Phelan CM, Claudio JO, Han FY, Chretien N, Rangaratnam S, MacCollin M, Short P, Parry D, Michels V, Riccardi VM, Weksberg R, Kitamura K, Bradburn JM, Hall BD, Propping P, Rouleau GA
American journal of human genetics. 1996 ; 59 (2) : 331-342.
PMID 8755919
 
A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor.
Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, Eldridge R, Kley N, Menon AG, Pulaski K
Cell. 1993 ; 72 (5) : 791-800.
PMID 8453669
 

Citation

This paper should be referenced as such :
Gusella, JF
NF2 (neurofibromatosis type 2)
Atlas Genet Cytogenet Oncol Haematol. 2001;5(2):91-92.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/NF2ID117.html
History of this paper:
Huret, JL. NF2 (neurofibromatosis type 2). Atlas Genet Cytogenet Oncol Haematol. 1998;2(2):39-40.
http://documents.irevues.inist.fr/bitstream/handle/2042/37406/03-1998-NF2117.pdf
Huret, JL. NF2 (neurofibromatosis type 2). Atlas Genet Cytogenet Oncol Haematol. 1998;2(2):39-40.
http://documents.irevues.inist.fr/bitstream/handle/2042/37406/03-1998-NF2117.pdf


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 22 ]
  Nervous system: Astrocytic tumors
Nervous system: Ependymomas
Nervous system: Meningioma
Malignant Mesothelioma
Nervous system: Peripheral nerve sheath tumors
Skin: Melanoma
Soft tissue tumors: an overview
Mesothelioma: t(14;22)(q32;q12) EWSR1/YY1
t(1;22)(p12;q12) NF2/HSD3B2
t(17;22)(q11;q12) NF2/RHOT1
t(17;22)(q11;q12) RHOT1/NF2
t(18;22)(p11;q12) NF2/PIEZO2
t(22;22)(q11;q12) GSTT1/NF2
t(22;22)(q11;q12) NF2/CLTCL1
t(22;22)(q11;q12) NF2/PI4KA
CABP7/NF2 (22q12)
EWSR1/NF2 (22q12)
NF2/CABP7 (22q12)
NF2/EIF3D (22q12)
t(22;22)(q12;q13) NF2/GRAP2
t(22;22)(q12;q13) NF2/TCF20
t(22;22)(q12;q13) TCF20/NF2


Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Neurofibromatosis type 2 (NF2)


External links

Nomenclature
Cards
AtlasNF2ID117.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)4771
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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indexed on : Thu Oct 18 17:45:10 CEST 2018

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