Mutational spectrum of the NF2 gene: a meta-analysis of 12 years of research and diagnostic laboratory findings
The NF2 tumor suppressor gene on chromosome 22 is a member of the protein 4.1 family of cytoskeletal elements. A number of single‐ and multiple‐tumor phenotypes have been linked to alterations of NF2 since its characterization in 1993. We present a meta‐analysis of 967 constitutional and somatic NF2...
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Published in | Human mutation Vol. 28; no. 1; pp. 1 - 12 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.01.2007
Hindawi Limited |
Subjects | |
Online Access | Get full text |
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Summary: | The NF2 tumor suppressor gene on chromosome 22 is a member of the protein 4.1 family of cytoskeletal elements. A number of single‐ and multiple‐tumor phenotypes have been linked to alterations of NF2 since its characterization in 1993. We present a meta‐analysis of 967 constitutional and somatic NF2 alterations from 93 published reports, along with 59 additional unpublished events identified in our laboratory and 115 alterations identified in clinical samples submitted to the Massachusetts General Hospital (MGH) Neurogenetics DNA Diagnostic Laboratory. In total, these sources defined 1,070 small genetic changes detected primarily by exon scanning, 42 intragenic changes of one whole exon or larger, and 29 whole gene deletions and gross chromosomal rearrangements. Constitutional single‐exon events (N=422) were significantly more likely to be nonsense or splice site changes than somatic events (N=533), which favored frameshift changes (χ2 test; P<0.001). Somatic events also differed markedly between tumors of different pathology, most significantly in the tendency of somatic events in meningiomas to lie within the 5′ FERM domain of the transcript (Fisher's exact test; P<0.01 in comparison to schwannomas) with a complete absence of mutations in exons 14 and 15. There was no statistically significant difference in mutation type or exon distribution between published constitutional events and those found by the clinical laboratory. Less than 10% of all published and unpublished small alterations are nontruncating (N=63) and these changes are clustered in exons 2 and 3, suggesting that this region may be especially crucial to tumor suppressor activity in the protein. Hum Mutat 28(1), 1–12, 2007. Published 2006 Wiley‐Liss, Inc. |
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Bibliography: | istex:3E39B2589B789E8B0E5F4359ED3B6D06AEE1BC6B ark:/67375/WNG-DR2F99DW-7 ArticleID:HUMU20393 Presented in part in abstract form at the 55th Annual Meeting of the American Society of Human Genetics, Salt Lake City, Utah, October, 2005. Supplementary Tables S1 and S2 National Institutes of Health - No. 1 R01 NS40527 Communicated by Jurgen Horst ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 |
ISSN: | 1059-7794 1098-1004 |
DOI: | 10.1002/humu.20393 |