Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were see...

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Main Authors:	Collisson, E., Campbell, J., Brooks, A., Berger, A., Lee, W., Chmielecki, J., Beer, D., Cope, L., Creighton, C., Danilova, L., Ding, L., Getz, G., Hammerman, P., Hayes, D., Hernandez, B., Herman, J., Heymach, J., Jurisica, I., Kucherlapati, R., Kwiatkowski, D., Ladanyi, M., Robertson, G., Schultz, N., Shen, R., Sinha, R., Sougnez, C., Tsao, M., Travis, W., Weinstein, J., Wigle, D., Wilkerson, M., Chu, A., Cherniack, A., Hadjipanayis, A., Rosenberg, M., Weisenberger, D., Laird, P., Radenbaugh, A., Ma, S., Stuart, J., Byers, L., Baylin, S., Govindan, R., Meyerson, M., Gabriel, S., Cibulskis, K., Kim, J., Stewart, C., Lichtenstein, L., Lander, E., Lawrence, M., Getz, E., Fulton, R., Fulton, L., McLellan, M., Wilson, R., Ye, K., Fronick, C., Maher, C., Miller, C., Wendl, M., Cabanski, C., Mardis, E., Wheeler, D., Balasundaram, M., Butterfield, Y., Carlsen, R., Chuah, E., Dhalla, N., Guin, R., Hirst, C., Lee, D., Li, H., Mayo, M., Moore, R., Mungall, A., Schein, J., Sipahimalani, P., Tam, A., Varhol, Richard, Robertson, A., Wye, N., Thiessen, N., Holt, R., Jones, S., Marra, M., Imielinski, M., Onofrio, R., Hodis, E., Zack, T., Helman, E.
Format:	Journal Article
Published:	Nature Publishing Group 2014
Online Access:	http://hdl.handle.net/20.500.11937/33734

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author	Collisson, E. Campbell, J. Brooks, A. Berger, A. Lee, W. Chmielecki, J. Beer, D. Cope, L. Creighton, C. Danilova, L. Ding, L. Getz, G. Hammerman, P. Hayes, D. Hernandez, B. Herman, J. Heymach, J. Jurisica, I. Kucherlapati, R. Kwiatkowski, D. Ladanyi, M. Robertson, G. Schultz, N. Shen, R. Sinha, R. Sougnez, C. Tsao, M. Travis, W. Weinstein, J. Wigle, D. Wilkerson, M. Chu, A. Cherniack, A. Hadjipanayis, A. Rosenberg, M. Weisenberger, D. Laird, P. Radenbaugh, A. Ma, S. Stuart, J. Byers, L. Baylin, S. Govindan, R. Meyerson, M. Gabriel, S. Cibulskis, K. Kim, J. Stewart, C. Lichtenstein, L. Lander, E. Lawrence, M. Getz, E. Fulton, R. Fulton, L. McLellan, M. Wilson, R. Ye, K. Fronick, C. Maher, C. Miller, C. Wendl, M. Cabanski, C. Mardis, E. Wheeler, D. Balasundaram, M. Butterfield, Y. Carlsen, R. Chuah, E. Dhalla, N. Guin, R. Hirst, C. Lee, D. Li, H. Mayo, M. Moore, R. Mungall, A. Schein, J. Sipahimalani, P. Tam, A. Varhol, Richard Robertson, A. Wye, N. Thiessen, N. Holt, R. Jones, S. Marra, M. Imielinski, M. Onofrio, R. Hodis, E. Zack, T. Helman, E.
author_facet	Collisson, E. Campbell, J. Brooks, A. Berger, A. Lee, W. Chmielecki, J. Beer, D. Cope, L. Creighton, C. Danilova, L. Ding, L. Getz, G. Hammerman, P. Hayes, D. Hernandez, B. Herman, J. Heymach, J. Jurisica, I. Kucherlapati, R. Kwiatkowski, D. Ladanyi, M. Robertson, G. Schultz, N. Shen, R. Sinha, R. Sougnez, C. Tsao, M. Travis, W. Weinstein, J. Wigle, D. Wilkerson, M. Chu, A. Cherniack, A. Hadjipanayis, A. Rosenberg, M. Weisenberger, D. Laird, P. Radenbaugh, A. Ma, S. Stuart, J. Byers, L. Baylin, S. Govindan, R. Meyerson, M. Gabriel, S. Cibulskis, K. Kim, J. Stewart, C. Lichtenstein, L. Lander, E. Lawrence, M. Getz, E. Fulton, R. Fulton, L. McLellan, M. Wilson, R. Ye, K. Fronick, C. Maher, C. Miller, C. Wendl, M. Cabanski, C. Mardis, E. Wheeler, D. Balasundaram, M. Butterfield, Y. Carlsen, R. Chuah, E. Dhalla, N. Guin, R. Hirst, C. Lee, D. Li, H. Mayo, M. Moore, R. Mungall, A. Schein, J. Sipahimalani, P. Tam, A. Varhol, Richard Robertson, A. Wye, N. Thiessen, N. Holt, R. Jones, S. Marra, M. Imielinski, M. Onofrio, R. Hodis, E. Zack, T. Helman, E.
author_sort	Collisson, E.
building	Curtin Institutional Repository
collection	Online Access
description	Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
first_indexed	2025-11-14T08:33:55Z
format	Journal Article
id	curtin-20.500.11937-33734
institution	Curtin University Malaysia
institution_category	Local University
last_indexed	2025-11-14T08:33:55Z
publishDate	2014
publisher	Nature Publishing Group
recordtype	eprints
repository_type	Digital Repository
spelling	curtin-20.500.11937-337342017-09-13T15:33:14Z Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network Collisson, E. Campbell, J. Brooks, A. Berger, A. Lee, W. Chmielecki, J. Beer, D. Cope, L. Creighton, C. Danilova, L. Ding, L. Getz, G. Hammerman, P. Hayes, D. Hernandez, B. Herman, J. Heymach, J. Jurisica, I. Kucherlapati, R. Kwiatkowski, D. Ladanyi, M. Robertson, G. Schultz, N. Shen, R. Sinha, R. Sougnez, C. Tsao, M. Travis, W. Weinstein, J. Wigle, D. Wilkerson, M. Chu, A. Cherniack, A. Hadjipanayis, A. Rosenberg, M. Weisenberger, D. Laird, P. Radenbaugh, A. Ma, S. Stuart, J. Byers, L. Baylin, S. Govindan, R. Meyerson, M. Gabriel, S. Cibulskis, K. Kim, J. Stewart, C. Lichtenstein, L. Lander, E. Lawrence, M. Getz, E. Fulton, R. Fulton, L. McLellan, M. Wilson, R. Ye, K. Fronick, C. Maher, C. Miller, C. Wendl, M. Cabanski, C. Mardis, E. Wheeler, D. Balasundaram, M. Butterfield, Y. Carlsen, R. Chuah, E. Dhalla, N. Guin, R. Hirst, C. Lee, D. Li, H. Mayo, M. Moore, R. Mungall, A. Schein, J. Sipahimalani, P. Tam, A. Varhol, Richard Robertson, A. Wye, N. Thiessen, N. Holt, R. Jones, S. Marra, M. Imielinski, M. Onofrio, R. Hodis, E. Zack, T. Helman, E. Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis. 2014 Journal Article http://hdl.handle.net/20.500.11937/33734 10.1038/nature13385 Nature Publishing Group fulltext
spellingShingle	Collisson, E. Campbell, J. Brooks, A. Berger, A. Lee, W. Chmielecki, J. Beer, D. Cope, L. Creighton, C. Danilova, L. Ding, L. Getz, G. Hammerman, P. Hayes, D. Hernandez, B. Herman, J. Heymach, J. Jurisica, I. Kucherlapati, R. Kwiatkowski, D. Ladanyi, M. Robertson, G. Schultz, N. Shen, R. Sinha, R. Sougnez, C. Tsao, M. Travis, W. Weinstein, J. Wigle, D. Wilkerson, M. Chu, A. Cherniack, A. Hadjipanayis, A. Rosenberg, M. Weisenberger, D. Laird, P. Radenbaugh, A. Ma, S. Stuart, J. Byers, L. Baylin, S. Govindan, R. Meyerson, M. Gabriel, S. Cibulskis, K. Kim, J. Stewart, C. Lichtenstein, L. Lander, E. Lawrence, M. Getz, E. Fulton, R. Fulton, L. McLellan, M. Wilson, R. Ye, K. Fronick, C. Maher, C. Miller, C. Wendl, M. Cabanski, C. Mardis, E. Wheeler, D. Balasundaram, M. Butterfield, Y. Carlsen, R. Chuah, E. Dhalla, N. Guin, R. Hirst, C. Lee, D. Li, H. Mayo, M. Moore, R. Mungall, A. Schein, J. Sipahimalani, P. Tam, A. Varhol, Richard Robertson, A. Wye, N. Thiessen, N. Holt, R. Jones, S. Marra, M. Imielinski, M. Onofrio, R. Hodis, E. Zack, T. Helman, E. Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network
title	Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network
title_full	Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network
title_fullStr	Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network
title_full_unstemmed	Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network
title_short	Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network
title_sort	comprehensive molecular profiling of lung adenocarcinoma: the cancer genome atlas research network
url	http://hdl.handle.net/20.500.11937/33734

Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network

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