The human epidermal growth factor receptor (EGFR) gene in European patients with advanced colorectal cancer harbors infrequent mutations in its tyrosine kinase domain.
BACKGROUND
The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptors, is a transmembrane tyrosine kinase (TK) activated by the binding of extracellular ligands of the EGF-family and involved in triggering the MAPK signaling pathway, which leads to cell proliferation. Mutations in the EGFR tyrosine kinase domain are frequent in non-small-cell lung cancer (NSCLC). However, to date, only very few, mainly non-European, studies have reported rare EGFR mutations in colorectal cancer (CRC).


METHODS
We screened 236 clinical tumor samples from European patients with advanced CRC by direct DNA sequencing to detect potential, as yet unknown mutations, in the EGFR gene exons 18 to 21, mainly covering the EGFR TK catalytic domain.


RESULTS
EGFR sequences showed somatic missense mutations in exons 18 and 20 at a frequency of 2.1% and 0.4% respectively. Somatic SNPs were also found in exons 20 and 21 at a frequency of about 3.1% and 0.4% respectively. Of these mutations, four have not yet been described elsewhere.


CONCLUSIONS
These mutation frequencies are higher than in a similarly sized population characterized by Barber and colleagues, but still too low to account for a major role played by the EGFR gene in CRC.
Laboratoire de Recherche sur le Cancer et les Maladies du Sang, Luxembourg, France.
Brigitte
B
Metzger
Laetitia
L
Chambeau
Dominique Y
DY
Begon
Carlo
C
Faber
Jacques
J
Kayser
Guy
G
Berchem
Marc
M
Pauly
Jacques
J
Boniver
Philippe
P
Delvenne
Mario
M
Dicato
Thomas
T
Wenner
D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D044465:White People / Q000235:genetics*
D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases