TY - JOUR
T1 - Genomic landscape of metastatic colorectal cancer
AU - Haan, Josien C.
AU - Labots, Mariette
AU - Rausch, Christian
AU - Koopman, Miriam
AU - Tol, Jolien
AU - Mekenkamp, Leonie J. M.
AU - van de Wiel, Mark A.
AU - Israeli, Danielle
AU - van Essen, Hendrik F.
AU - van Grieken, Nicole C. T.
AU - Voorham, Quirinus J. M.
AU - Bosch, Linda J. W.
AU - Qu, Xueping
AU - Kabbarah, Omar
AU - Verheul, Henk M. W.
AU - Nagtegaal, Iris D.
AU - Punt, Cornelis J. A.
AU - Ylstra, Bauke
AU - Meijer, Gerrit A.
PY - 2014
Y1 - 2014
N2 - Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumour biology. Here we describe the genomic landscape of tumour samples of a homogeneous well-annotated series of patients with metastatic CRC (mCRC) of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations of 349 patients are determined. Within three treatment arms, 194 chromosomal subregions are associated with progression-free survival (PFS; uncorrected single-test P-values <0.005). These subregions are filtered for effect on messenger RNA expression, using an independent data set from The Cancer Genome Atlas which returned 171 genes. Three chromosomal regions are associated with a significant difference in PFS between treatment arms with or without irinotecan. One of these regions, 6q16.1-q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape of mCRC reveals a number of DNA copy number aberrations associated with response to drug therapy
AB - Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumour biology. Here we describe the genomic landscape of tumour samples of a homogeneous well-annotated series of patients with metastatic CRC (mCRC) of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations of 349 patients are determined. Within three treatment arms, 194 chromosomal subregions are associated with progression-free survival (PFS; uncorrected single-test P-values <0.005). These subregions are filtered for effect on messenger RNA expression, using an independent data set from The Cancer Genome Atlas which returned 171 genes. Three chromosomal regions are associated with a significant difference in PFS between treatment arms with or without irinotecan. One of these regions, 6q16.1-q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape of mCRC reveals a number of DNA copy number aberrations associated with response to drug therapy
U2 - https://doi.org/10.1038/ncomms6457
DO - https://doi.org/10.1038/ncomms6457
M3 - Article
C2 - 25394515
SN - 2041-1723
VL - 5
SP - 5457
JO - Nature Communications
JF - Nature Communications
M1 - 5457
ER -