Integrated genomic characterization of endometrial carcinoma

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array-and sequencing-based technologies. Uterine serous tumours and ~25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oe...

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Main Authors:	Getz, G., Gabriel, S., Cibulskis, K., Lander, E., Sivachenko, A., Sougnez, C., Lawrence, M., Kandoth, C., Dooling, D., Fulton, R., Fulton, L., Kalicki-Veizer, J., McLellan, M., O'Laughlin, M., Schmidt, H., Wilson, R., Ye, K., Li, D., Ally, A., Balasundaram, M., Birol, I., Butterfield, Y., Carlsen, R., Carter, C., Chu, A., Chuah, E., Chun, H., Dhalla, N., Guin, R., Hirst, C., Holt, R., Jones, S., Lee, D., Li, H., Marra, M., Mayo, M., Moore, R., Mungall, A., Plettner, P., Schein, J., Sipahimalani, P., Tam, A., Varhol, Richard, Gordon Robertson, A., Cherniack, A., Pashtan, I., Saksena, G., Onofrio, R., Schumacher, S., Tabak, B., Carter, S., Hernandez, B., Gentry, J., Salvesen, H., Ardlie, K., Winckler, W., Beroukhim, R., Meyerson, M., Hadjipanayis, A., Lee, S., Mahadeshwar, H., Park, P., Protopopov, A., Ren, X., Seth, S., Song, X., Tang, J., Xi, R., Yang, L., Dong, Z., Kucherlapati, R., Chin, L., Zhang, J., Todd Auman, J., Balu, S., Bodenheimer, T., Buda, E., Neil Hayes, D., Hoyle, A., Jefferys, S., Jones, C., Meng, S., Mieczkowski, P., Mose, L., Parker, J., Perou, C.
Format:	Journal Article
Published:	2013
Online Access:	http://hdl.handle.net/20.500.11937/43955

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author	Getz, G. Gabriel, S. Cibulskis, K. Lander, E. Sivachenko, A. Sougnez, C. Lawrence, M. Kandoth, C. Dooling, D. Fulton, R. Fulton, L. Kalicki-Veizer, J. McLellan, M. O'Laughlin, M. Schmidt, H. Wilson, R. Ye, K. Li, D. Ally, A. Balasundaram, M. Birol, I. Butterfield, Y. Carlsen, R. Carter, C. Chu, A. Chuah, E. Chun, H. Dhalla, N. Guin, R. Hirst, C. Holt, R. Jones, S. Lee, D. Li, H. Marra, M. Mayo, M. Moore, R. Mungall, A. Plettner, P. Schein, J. Sipahimalani, P. Tam, A. Varhol, Richard Gordon Robertson, A. Cherniack, A. Pashtan, I. Saksena, G. Onofrio, R. Schumacher, S. Tabak, B. Carter, S. Hernandez, B. Gentry, J. Salvesen, H. Ardlie, K. Winckler, W. Beroukhim, R. Meyerson, M. Hadjipanayis, A. Lee, S. Mahadeshwar, H. Park, P. Protopopov, A. Ren, X. Seth, S. Song, X. Tang, J. Xi, R. Yang, L. Dong, Z. Kucherlapati, R. Chin, L. Zhang, J. Todd Auman, J. Balu, S. Bodenheimer, T. Buda, E. Neil Hayes, D. Hoyle, A. Jefferys, S. Jones, C. Meng, S. Mieczkowski, P. Mose, L. Parker, J. Perou, C.
author_facet	Getz, G. Gabriel, S. Cibulskis, K. Lander, E. Sivachenko, A. Sougnez, C. Lawrence, M. Kandoth, C. Dooling, D. Fulton, R. Fulton, L. Kalicki-Veizer, J. McLellan, M. O'Laughlin, M. Schmidt, H. Wilson, R. Ye, K. Li, D. Ally, A. Balasundaram, M. Birol, I. Butterfield, Y. Carlsen, R. Carter, C. Chu, A. Chuah, E. Chun, H. Dhalla, N. Guin, R. Hirst, C. Holt, R. Jones, S. Lee, D. Li, H. Marra, M. Mayo, M. Moore, R. Mungall, A. Plettner, P. Schein, J. Sipahimalani, P. Tam, A. Varhol, Richard Gordon Robertson, A. Cherniack, A. Pashtan, I. Saksena, G. Onofrio, R. Schumacher, S. Tabak, B. Carter, S. Hernandez, B. Gentry, J. Salvesen, H. Ardlie, K. Winckler, W. Beroukhim, R. Meyerson, M. Hadjipanayis, A. Lee, S. Mahadeshwar, H. Park, P. Protopopov, A. Ren, X. Seth, S. Song, X. Tang, J. Xi, R. Yang, L. Dong, Z. Kucherlapati, R. Chin, L. Zhang, J. Todd Auman, J. Balu, S. Bodenheimer, T. Buda, E. Neil Hayes, D. Hoyle, A. Jefferys, S. Jones, C. Meng, S. Mieczkowski, P. Mose, L. Parker, J. Perou, C.
author_sort	Getz, G.
building	Curtin Institutional Repository
collection	Online Access
description	We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array-and sequencing-based technologies. Uterine serous tumours and ~25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours. © 2013 Macmillan Publishers Limited. All rights reserved.
first_indexed	2025-11-14T09:18:53Z
format	Journal Article
id	curtin-20.500.11937-43955
institution	Curtin University Malaysia
institution_category	Local University
last_indexed	2025-11-14T09:18:53Z
publishDate	2013
recordtype	eprints
repository_type	Digital Repository
spelling	curtin-20.500.11937-439552017-09-13T14:02:52Z Integrated genomic characterization of endometrial carcinoma Getz, G. Gabriel, S. Cibulskis, K. Lander, E. Sivachenko, A. Sougnez, C. Lawrence, M. Kandoth, C. Dooling, D. Fulton, R. Fulton, L. Kalicki-Veizer, J. McLellan, M. O'Laughlin, M. Schmidt, H. Wilson, R. Ye, K. Li, D. Ally, A. Balasundaram, M. Birol, I. Butterfield, Y. Carlsen, R. Carter, C. Chu, A. Chuah, E. Chun, H. Dhalla, N. Guin, R. Hirst, C. Holt, R. Jones, S. Lee, D. Li, H. Marra, M. Mayo, M. Moore, R. Mungall, A. Plettner, P. Schein, J. Sipahimalani, P. Tam, A. Varhol, Richard Gordon Robertson, A. Cherniack, A. Pashtan, I. Saksena, G. Onofrio, R. Schumacher, S. Tabak, B. Carter, S. Hernandez, B. Gentry, J. Salvesen, H. Ardlie, K. Winckler, W. Beroukhim, R. Meyerson, M. Hadjipanayis, A. Lee, S. Mahadeshwar, H. Park, P. Protopopov, A. Ren, X. Seth, S. Song, X. Tang, J. Xi, R. Yang, L. Dong, Z. Kucherlapati, R. Chin, L. Zhang, J. Todd Auman, J. Balu, S. Bodenheimer, T. Buda, E. Neil Hayes, D. Hoyle, A. Jefferys, S. Jones, C. Meng, S. Mieczkowski, P. Mose, L. Parker, J. Perou, C. We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array-and sequencing-based technologies. Uterine serous tumours and ~25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours. © 2013 Macmillan Publishers Limited. All rights reserved. 2013 Journal Article http://hdl.handle.net/20.500.11937/43955 10.1038/nature12113 fulltext
spellingShingle	Getz, G. Gabriel, S. Cibulskis, K. Lander, E. Sivachenko, A. Sougnez, C. Lawrence, M. Kandoth, C. Dooling, D. Fulton, R. Fulton, L. Kalicki-Veizer, J. McLellan, M. O'Laughlin, M. Schmidt, H. Wilson, R. Ye, K. Li, D. Ally, A. Balasundaram, M. Birol, I. Butterfield, Y. Carlsen, R. Carter, C. Chu, A. Chuah, E. Chun, H. Dhalla, N. Guin, R. Hirst, C. Holt, R. Jones, S. Lee, D. Li, H. Marra, M. Mayo, M. Moore, R. Mungall, A. Plettner, P. Schein, J. Sipahimalani, P. Tam, A. Varhol, Richard Gordon Robertson, A. Cherniack, A. Pashtan, I. Saksena, G. Onofrio, R. Schumacher, S. Tabak, B. Carter, S. Hernandez, B. Gentry, J. Salvesen, H. Ardlie, K. Winckler, W. Beroukhim, R. Meyerson, M. Hadjipanayis, A. Lee, S. Mahadeshwar, H. Park, P. Protopopov, A. Ren, X. Seth, S. Song, X. Tang, J. Xi, R. Yang, L. Dong, Z. Kucherlapati, R. Chin, L. Zhang, J. Todd Auman, J. Balu, S. Bodenheimer, T. Buda, E. Neil Hayes, D. Hoyle, A. Jefferys, S. Jones, C. Meng, S. Mieczkowski, P. Mose, L. Parker, J. Perou, C. Integrated genomic characterization of endometrial carcinoma
title	Integrated genomic characterization of endometrial carcinoma
title_full	Integrated genomic characterization of endometrial carcinoma
title_fullStr	Integrated genomic characterization of endometrial carcinoma
title_full_unstemmed	Integrated genomic characterization of endometrial carcinoma
title_short	Integrated genomic characterization of endometrial carcinoma
title_sort	integrated genomic characterization of endometrial carcinoma
url	http://hdl.handle.net/20.500.11937/43955

Integrated genomic characterization of endometrial carcinoma

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