Colorectal liver metastases are more often super wild type. Toward treatment based on metastatic site genotyping?

Recent data showed that metastatic colorectal (mCRC) tumors exhibiting extended RAS-BRAF mutations were resistant to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, making these drugs suitable for the so-called “super” wild-type (WT) patients only. This study aimed to compare the...

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Bibliographic Details
Published in:Targeted oncology 2015-09, Vol.10 (3), p.415-421
Main Authors: Allard, M. A., Saffroy, R., de la Maisonneuve, P. Bouvet, Ricca, L., Bosselut, N., Hamelin, J., Lecorche, E., Bejarano, M. A., Innominato, P., Sebagh, M., Adam, R., Morère, J. F., Lemoine, A.
Format: Article
Language:English
Subjects:
Aged
Biomedicine
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
DNA Mutational Analysis
Exons
Female
Genotype
GTP Phosphohydrolases - genetics
Humans
Liver Neoplasms - genetics
Liver Neoplasms - secondary
Male
Medicine
Medicine & Public Health
Membrane Proteins - genetics
Middle Aged
Multivariate Analysis
Mutation
Neoplasm Metastasis
Oncology
Original Research
Prevalence
Proto-Oncogene Proteins B-raf - genetics
Proto-Oncogene Proteins p21(ras) - genetics
Regression Analysis
Signal Transduction
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Summary:Recent data showed that metastatic colorectal (mCRC) tumors exhibiting extended RAS-BRAF mutations were resistant to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, making these drugs suitable for the so-called “super” wild-type (WT) patients only. This study aimed to compare the extended RAS-BRAF mutation frequency and characteristics according to location of tumor sampling. All consecutive mCRC specimens ( N  = 1659) referred to our institution from January 2008 till June 2014 were included in the analysis. Tumor genotyping (first for KRAS exon 2, then for BRAF exon 15, and later for KRAS exons 2, 3, and 4 and NRAS exons 2, 3, and 4) was performed with high-resolution melting analysis or allelic discrimination. The factors predicting for the presence of mutation were explored using multivariate binary logistic regression. Overall, the prevalence of KRAS exon 2 was 36.8 %, and it was lower in liver metastases ( N  = 138/490; 28.2 %) in comparison with primary tumors ( N  = 442/1086; 40.7 %), lung metastases (16/32; 50 %), or other metastatic sites (15/51; 29.4 %; P  
ISSN:1776-2596
1776-260X
DOI:10.1007/s11523-014-0346-5