Genomic landscape of metastatic colorectal cancer

Josien C. Haan; Mariette Labots; Christian Rausch; Miriam Koopman; Jolien Tol; Leonie J. M. Mekenkamp; Mark A. van de Wiel; Danielle Israeli; Hendrik F. van Essen; Nicole C. T. van Grieken; Quirinus J. M. Voorham; Linda J. W. Bosch; Xueping Qu; Omar Kabbarah; Henk M. W. Verheul; Iris D. Nagtegaal; Cornelis J. A. Punt; Bauke Ylstra; Gerrit A. Meijer

doi:https://doi.org/10.1038/ncomms6457

Genomic landscape of metastatic colorectal cancer

Josien C. Haan, Mariette Labots, Christian Rausch, Miriam Koopman, Jolien Tol, Leonie J. M. Mekenkamp, Mark A. van de Wiel, Danielle Israeli, Hendrik F. van Essen, Nicole C. T. van Grieken, Quirinus J. M. Voorham, Linda J. W. Bosch, Xueping Qu, Omar Kabbarah, Henk M. W. Verheul, Iris D. Nagtegaal, Cornelis J. A. Punt, Bauke Ylstra, Gerrit A. Meijer

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Abstract

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

Original language	English
Article number	5457
Pages (from-to)	5457
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6457
Publication status	Published - 2014

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https://doi.org/10.1038/ncomms6457

Cite this

Haan, J. C., Labots, M., Rausch, C., Koopman, M., Tol, J., Mekenkamp, L. J. M., van de Wiel, M. A., Israeli, D., van Essen, H. F., van Grieken, N. C. T., Voorham, Q. J. M., Bosch, L. J. W., Qu, X., Kabbarah, O., Verheul, H. M. W., Nagtegaal, I. D., Punt, C. J. A., Ylstra, B., & Meijer, G. A. (2014). Genomic landscape of metastatic colorectal cancer. Nature communications, 5, 5457. [5457]. https://doi.org/10.1038/ncomms6457

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title = "Genomic landscape of metastatic colorectal cancer",

abstract = "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",

author = "Haan, {Josien C.} and Mariette Labots and Christian Rausch and Miriam Koopman and Jolien Tol and Mekenkamp, {Leonie J. M.} and {van de Wiel}, {Mark A.} and Danielle Israeli and {van Essen}, {Hendrik F.} and {van Grieken}, {Nicole C. T.} and Voorham, {Quirinus J. M.} and Bosch, {Linda J. W.} and Xueping Qu and Omar Kabbarah and Verheul, {Henk M. W.} and Nagtegaal, {Iris D.} and Punt, {Cornelis J. A.} and Bauke Ylstra and Meijer, {Gerrit A.}",

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Haan, JC, Labots, M, Rausch, C, Koopman, M, Tol, J, Mekenkamp, LJM, van de Wiel, MA, Israeli, D, van Essen, HF, van Grieken, NCT, Voorham, QJM, Bosch, LJW, Qu, X, Kabbarah, O, Verheul, HMW, Nagtegaal, ID, Punt, CJA , Ylstra, B & Meijer, GA 2014, 'Genomic landscape of metastatic colorectal cancer', Nature communications, vol. 5, 5457, pp. 5457. https://doi.org/10.1038/ncomms6457

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AU - Haan, Josien C.

AU - Labots, Mariette

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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.

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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

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