Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
16873291
TITLE
Rapid screening of 4000 individuals for germ-line variations in the BRAF gene.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
The BRAF gene is frequently somatically altered in malignant melanoma. A majority of variations are at the valine 600 residue leading to a V600E substitution that constitutively activates the kinase. We screened 4000 patient and control DNAs for germ-line variations at the valine 600 residue.
METHODS NlmCategory: METHODS
We developed a novel assay by adapting single-base variation assays and software for MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry to screen for all 5 reported variants at codon 600 of the BRAF gene. We screened a case-control collection comprising samples from 1082 melanoma patients and 154 of their unaffected relatives from 1278 families and from 2744 individuals from 659 unselected twin families with no history of melanoma. A panel of 66 melanoma cell lines was used for variation-positive controls.
RESULTS NlmCategory: RESULTS
All melanoma cell lines that we had found previously to carry a codon 600 variation were verified in this study. Three of the 4 possible variants (V600E n = 47, V600K n = 2, V600R n = 1) were detected, but no case of V600D was available. No germ-line variants were found in the samples from the 3980 melanoma patients or from the control individuals.
CONCLUSIONS NlmCategory: CONCLUSIONS
This new assay is a high-throughput, automated alternative to standard sequencing and can be used as a rapid initial screen for somatic variants associated with melanoma. Germ-line variants at valine 600 are unlikely to exist and do not contribute to the reported role of the BRAF gene in melanoma predisposition.
DATE PUBLISHED
2006 Sep
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2006/07/27
pubmed 2006/07/29 09:00
medline 2006/09/29 09:00
entrez 2006/07/29 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
James MR James Michael R MR Queensland Institute of Medical Research, Brisbane, Australia. michaelJ@qimr.edu.au
Dumeni T Dumeni Troy T
Stark MS Stark Mitchell S MS
Duffy DL Duffy David L DL
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Hayward NK Hayward Nicholas K NK
INVESTIGATORS
JOURNAL
VOLUME: 52
ISSUE: 9
TITLE: Clinical chemistry
ISOABBREVIATION: Clin. Chem.
YEAR: 2006
MONTH: Sep
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0009-9147
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Clin Chem
COUNTRY: United States
ISSNLINKING: 0009-9147
NLMUNIQUEID: 9421549
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
CA88363 NCI NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Case-Control Studies
Cell Line, Tumor
Genetic Predisposition to Disease
Genetic Testing
Genotype
Germ-Line Mutation
Humans
Melanoma genetics
Polymerase Chain Reaction genetics
Proto-Oncogene Proteins B-raf genetics
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
EC 2.7.11.1 BRAF protein, human
EC 2.7.11.1 Proto-Oncogene Proteins B-raf
OTHER ID's