Comprehensive molecular characterization of human colon and rectal cancer

To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome seq...

Full description

Bibliographic Details
Main Authors:	Muzny, D., Bainbridge, M., Chang, K., Dinh, H., Drummond, J., Fowler, G., Kovar, C., Lewis, L., Morgan, M., Newsham, I., Reid, J., Santibanez, J., Shinbrot, E., Trevino, L., Wu, Y., Wang, M., Gunaratne, P., Donehower, L., Creighton, C., Wheeler, D., Gibbs, R., Lawrence, M., Voet, D., Jing, R., Cibulskis, K., Sivachenko, A., Stojanov, P., McKenna, A., Lander, E., Gabriel, S., Ding, L., Fulton, R., Koboldt, D., Wylie, T., Walker, J., Dooling, D., Fulton, L., Delehaunty, K., Fronick, C., Demeter, R., Mardis, E., Wilson, R., Chu, A., Chun, H., Mungall, A., Pleasance, E., Gordon Robertson, A., Stoll, D., Balasundaram, M., Birol, I., Butterfield, Y., Chuah, E., Coope, R., Dhalla, N., Guin, R., Hirst, C., Hirst, M., Holt, R., Lee, D., Li, H., Mayo, M., Moore, R., Schein, J., Slobodan, J., Tam, A., Thiessen, N., Varhol, Richard, Zeng, T., Zhao, Y., Jones, S., Marra, M., Bass, A., Ramos, A., Saksena, G., Cherniack, A., Schumacher, S., Tabak, B., Carter, S., Pho, N., Nguyen, H., Onofrio, R., Crenshaw, A., Ardlie, K.
Format:	Journal Article
Published:	2012
Online Access:	http://hdl.handle.net/20.500.11937/27655

_version_	1848752324141383680
author	Muzny, D. Bainbridge, M. Chang, K. Dinh, H. Drummond, J. Fowler, G. Kovar, C. Lewis, L. Morgan, M. Newsham, I. Reid, J. Santibanez, J. Shinbrot, E. Trevino, L. Wu, Y. Wang, M. Gunaratne, P. Donehower, L. Creighton, C. Wheeler, D. Gibbs, R. Lawrence, M. Voet, D. Jing, R. Cibulskis, K. Sivachenko, A. Stojanov, P. McKenna, A. Lander, E. Gabriel, S. Ding, L. Fulton, R. Koboldt, D. Wylie, T. Walker, J. Dooling, D. Fulton, L. Delehaunty, K. Fronick, C. Demeter, R. Mardis, E. Wilson, R. Chu, A. Chun, H. Mungall, A. Pleasance, E. Gordon Robertson, A. Stoll, D. Balasundaram, M. Birol, I. Butterfield, Y. Chuah, E. Coope, R. Dhalla, N. Guin, R. Hirst, C. Hirst, M. Holt, R. Lee, D. Li, H. Mayo, M. Moore, R. Schein, J. Slobodan, J. Tam, A. Thiessen, N. Varhol, Richard Zeng, T. Zhao, Y. Jones, S. Marra, M. Bass, A. Ramos, A. Saksena, G. Cherniack, A. Schumacher, S. Tabak, B. Carter, S. Pho, N. Nguyen, H. Onofrio, R. Crenshaw, A. Ardlie, K.
author_facet	Muzny, D. Bainbridge, M. Chang, K. Dinh, H. Drummond, J. Fowler, G. Kovar, C. Lewis, L. Morgan, M. Newsham, I. Reid, J. Santibanez, J. Shinbrot, E. Trevino, L. Wu, Y. Wang, M. Gunaratne, P. Donehower, L. Creighton, C. Wheeler, D. Gibbs, R. Lawrence, M. Voet, D. Jing, R. Cibulskis, K. Sivachenko, A. Stojanov, P. McKenna, A. Lander, E. Gabriel, S. Ding, L. Fulton, R. Koboldt, D. Wylie, T. Walker, J. Dooling, D. Fulton, L. Delehaunty, K. Fronick, C. Demeter, R. Mardis, E. Wilson, R. Chu, A. Chun, H. Mungall, A. Pleasance, E. Gordon Robertson, A. Stoll, D. Balasundaram, M. Birol, I. Butterfield, Y. Chuah, E. Coope, R. Dhalla, N. Guin, R. Hirst, C. Hirst, M. Holt, R. Lee, D. Li, H. Mayo, M. Moore, R. Schein, J. Slobodan, J. Tam, A. Thiessen, N. Varhol, Richard Zeng, T. Zhao, Y. Jones, S. Marra, M. Bass, A. Ramos, A. Saksena, G. Cherniack, A. Schumacher, S. Tabak, B. Carter, S. Pho, N. Nguyen, H. Onofrio, R. Crenshaw, A. Ardlie, K.
author_sort	Muzny, D.
building	Curtin Institutional Repository
collection	Online Access
description	To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase µ (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. © 2012 Macmillan Publishers Limited. All rights reserved.
first_indexed	2025-11-14T08:06:48Z
format	Journal Article
id	curtin-20.500.11937-27655
institution	Curtin University Malaysia
institution_category	Local University
last_indexed	2025-11-14T08:06:48Z
publishDate	2012
recordtype	eprints
repository_type	Digital Repository
spelling	curtin-20.500.11937-276552017-09-13T15:06:34Z Comprehensive molecular characterization of human colon and rectal cancer Muzny, D. Bainbridge, M. Chang, K. Dinh, H. Drummond, J. Fowler, G. Kovar, C. Lewis, L. Morgan, M. Newsham, I. Reid, J. Santibanez, J. Shinbrot, E. Trevino, L. Wu, Y. Wang, M. Gunaratne, P. Donehower, L. Creighton, C. Wheeler, D. Gibbs, R. Lawrence, M. Voet, D. Jing, R. Cibulskis, K. Sivachenko, A. Stojanov, P. McKenna, A. Lander, E. Gabriel, S. Ding, L. Fulton, R. Koboldt, D. Wylie, T. Walker, J. Dooling, D. Fulton, L. Delehaunty, K. Fronick, C. Demeter, R. Mardis, E. Wilson, R. Chu, A. Chun, H. Mungall, A. Pleasance, E. Gordon Robertson, A. Stoll, D. Balasundaram, M. Birol, I. Butterfield, Y. Chuah, E. Coope, R. Dhalla, N. Guin, R. Hirst, C. Hirst, M. Holt, R. Lee, D. Li, H. Mayo, M. Moore, R. Schein, J. Slobodan, J. Tam, A. Thiessen, N. Varhol, Richard Zeng, T. Zhao, Y. Jones, S. Marra, M. Bass, A. Ramos, A. Saksena, G. Cherniack, A. Schumacher, S. Tabak, B. Carter, S. Pho, N. Nguyen, H. Onofrio, R. Crenshaw, A. Ardlie, K. To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase µ (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. © 2012 Macmillan Publishers Limited. All rights reserved. 2012 Journal Article http://hdl.handle.net/20.500.11937/27655 10.1038/nature11252 fulltext
spellingShingle	Muzny, D. Bainbridge, M. Chang, K. Dinh, H. Drummond, J. Fowler, G. Kovar, C. Lewis, L. Morgan, M. Newsham, I. Reid, J. Santibanez, J. Shinbrot, E. Trevino, L. Wu, Y. Wang, M. Gunaratne, P. Donehower, L. Creighton, C. Wheeler, D. Gibbs, R. Lawrence, M. Voet, D. Jing, R. Cibulskis, K. Sivachenko, A. Stojanov, P. McKenna, A. Lander, E. Gabriel, S. Ding, L. Fulton, R. Koboldt, D. Wylie, T. Walker, J. Dooling, D. Fulton, L. Delehaunty, K. Fronick, C. Demeter, R. Mardis, E. Wilson, R. Chu, A. Chun, H. Mungall, A. Pleasance, E. Gordon Robertson, A. Stoll, D. Balasundaram, M. Birol, I. Butterfield, Y. Chuah, E. Coope, R. Dhalla, N. Guin, R. Hirst, C. Hirst, M. Holt, R. Lee, D. Li, H. Mayo, M. Moore, R. Schein, J. Slobodan, J. Tam, A. Thiessen, N. Varhol, Richard Zeng, T. Zhao, Y. Jones, S. Marra, M. Bass, A. Ramos, A. Saksena, G. Cherniack, A. Schumacher, S. Tabak, B. Carter, S. Pho, N. Nguyen, H. Onofrio, R. Crenshaw, A. Ardlie, K. Comprehensive molecular characterization of human colon and rectal cancer
title	Comprehensive molecular characterization of human colon and rectal cancer
title_full	Comprehensive molecular characterization of human colon and rectal cancer
title_fullStr	Comprehensive molecular characterization of human colon and rectal cancer
title_full_unstemmed	Comprehensive molecular characterization of human colon and rectal cancer
title_short	Comprehensive molecular characterization of human colon and rectal cancer
title_sort	comprehensive molecular characterization of human colon and rectal cancer
url	http://hdl.handle.net/20.500.11937/27655

Comprehensive molecular characterization of human colon and rectal cancer

Similar Items