TY - JOUR
T1 - RAS testing in metastatic colorectal cancer: excellent reproducibility amongst 17 Dutch pathology centers
AU - Boleij, Annemarie
AU - Tops, Bastiaan B. J.
AU - Rombout, Paul D. M.
AU - Dequeker, Elizabeth M.
AU - Ligtenberg, Marjolijn J. L.
AU - van Krieken, J. Han
AU - Heideman, D.A.M.
PY - 2015
Y1 - 2015
N2 - In 2013 the European Medicine Agency (EMA) restricted the indication for anti-EGFR targeted therapy to metastatic colorectal cancer (mCRC) with a wild-type RAS gene, increasing the need for reliable RAS mutation testing. We evaluated the completeness and reproducibility of RAS-testing in the Netherlands. From 17 laboratories, tumor DNA of the first 10 CRC cases tested in 2014 in routine clinical practice was re-tested by a reference laboratory using a custom next generation sequencing panel. In total, 171 CRC cases were re-evaluated for hotspot mutations in KRAS, NRAS and BRAF. Most laboratories had introduced complete RAS-testing (65%) and BRAF-testing (71%) by January 2014. The most employed method for all hotspot regions was Sanger sequencing (range 35.7 - 49.2%). The reference laboratory detected all mutations that had been found in the participating laboratories (n = 92), plus 10 additional mutations. This concerned three RAS and seven BRAF mutations that were missed due to incomplete testing of the participating laboratory. Overall, the concordance of tests performed by both the reference and participating laboratory was 100% (163/163; κ-static 1.0) for RAS and 100% (144/144; κ-static 1.0) for BRAF. Our study shows that RAS and BRAF mutations can be reproducibly assessed using a variety of testing methods
AB - In 2013 the European Medicine Agency (EMA) restricted the indication for anti-EGFR targeted therapy to metastatic colorectal cancer (mCRC) with a wild-type RAS gene, increasing the need for reliable RAS mutation testing. We evaluated the completeness and reproducibility of RAS-testing in the Netherlands. From 17 laboratories, tumor DNA of the first 10 CRC cases tested in 2014 in routine clinical practice was re-tested by a reference laboratory using a custom next generation sequencing panel. In total, 171 CRC cases were re-evaluated for hotspot mutations in KRAS, NRAS and BRAF. Most laboratories had introduced complete RAS-testing (65%) and BRAF-testing (71%) by January 2014. The most employed method for all hotspot regions was Sanger sequencing (range 35.7 - 49.2%). The reference laboratory detected all mutations that had been found in the participating laboratories (n = 92), plus 10 additional mutations. This concerned three RAS and seven BRAF mutations that were missed due to incomplete testing of the participating laboratory. Overall, the concordance of tests performed by both the reference and participating laboratory was 100% (163/163; κ-static 1.0) for RAS and 100% (144/144; κ-static 1.0) for BRAF. Our study shows that RAS and BRAF mutations can be reproducibly assessed using a variety of testing methods
U2 - https://doi.org/10.18632/oncotarget.3804
DO - https://doi.org/10.18632/oncotarget.3804
M3 - Article
C2 - 25944693
SN - 1949-2553
VL - 6
SP - 15681
EP - 15689
JO - Oncotarget
JF - Oncotarget
IS - 17
ER -