Document Detail


Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome.
MedLine Citation:
PMID:  20735442     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
BRAF, the protein product of BRAF, is a serine/threonine protein kinase and one of the direct downstream effectors of Ras. Somatic mutations in BRAF occur in numerous human cancers, whereas germline BRAF mutations cause cardio-facio-cutaneous (CFC) syndrome. One recurrent somatic mutation, p.V600E, is frequently found in several tumor types, such as melanoma, papillary thyroid carcinoma, colon cancer, and ovarian cancer. However, a germline mutation affecting codon 600 has never been described. Here, we present a patient with CFC syndrome and a de novo germline mutation involving codon 600 of BRAF, thus providing the first evidence that a pathogenic germline mutation involving this critical codon is not only compatible with development but can also cause the CFC phenotype. In vitro functional analysis shows that this mutation, which replaces a valine with a glycine at codon 600 (p.V600G), leads to increased ERK and ELK phosphorylation compared to wild-type BRAF but is less strongly activating than the cancer-associated p.V600E mutation.
Authors:
K J Champion; C Bunag; A L Estep; J R Jones; C H Bolt; R C Rogers; K A Rauen; D B Everman
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical genetics     Volume:  79     ISSN:  1399-0004     ISO Abbreviation:  Clin. Genet.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0253664     Medline TA:  Clin Genet     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  468-74     Citation Subset:  IM    
Copyright Information:
© 2010 John Wiley & Sons A/S.
Affiliation:
Greenwood Genetic Center, Greenwood, SC 29646, USA.
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MeSH Terms
Descriptor/Qualifier:
Grant Support
ID/Acronym/Agency:
HD048502/HD/NICHD NIH HHS; UL1 RR024131/RR/NCRR NIH HHS

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