Integrated genomic characterization of oesophageal carcinoma

Jihun Kim; Reanne Bowlby; Andrew J. Mungall; A. Gordon Robertson; Robert D. Odze; Andrew D. Cherniack; Juliann Shih; Chandra Sekhar Pedamallu; Carrie Cibulskis; Andrew Dunford; Samuel R. Meier; Jaegil Kim; J. Raphael; Hsin Ta Wu; Alexandra M. Wong; Joseph E. Willis; Adam J. Bass; Sarah Derks; Katherine Garman; Shannon J. McCall; MacIej Wiznerowicz; Angeliki Pantazi; Michael Parfenov; Vésteinn Thorsson; Ilya Shmulevich; Varsha Dhankani; Michael Miller; Ku Leuven Ryo Sakai; Kenneth Wang; Nikolaus Schultz; Ronglai Shen; Arshi Arora; Nils Weinhold; Francisco Sánchez-Vega; David P. Kelsen; Julia Zhang; Ina Felau; John Demchok; Charles S. Rabkin; M. Constanza Camargo; Jean Claude Zenklusen; Jay Bowen; Kristen Leraas; Tara M. Lichtenberg; Christina Curtis; Jose A. Seoane; Akinyemi I. Ojesina; David G. Beer; Frank Carey; Ian Forgie; The Cancer Genome Atlas Research Network

doi:10.1038/nature20805

Integrated genomic characterization of oesophageal carcinoma

Jihun Kim, Reanne Bowlby, Andrew J. Mungall, A. Gordon Robertson, Robert D. Odze, Andrew D. Cherniack, Juliann Shih, Chandra Sekhar Pedamallu, Carrie Cibulskis, Andrew Dunford, Samuel R. Meier, Jaegil Kim, J. Raphael, Hsin Ta Wu, Alexandra M. Wong, Joseph E. Willis, Adam J. Bass (Lead / Corresponding author), Sarah Derks, Katherine Garman, Shannon J. McCallMacIej Wiznerowicz, Angeliki Pantazi, Michael Parfenov, Vésteinn Thorsson (Lead / Corresponding author), Ilya Shmulevich, Varsha Dhankani, Michael Miller, Ku Leuven Ryo Sakai, Kenneth Wang, Nikolaus Schultz, Ronglai Shen, Arshi Arora, Nils Weinhold, Francisco Sánchez-Vega, David P. Kelsen, Julia Zhang, Ina Felau, John Demchok, Charles S. Rabkin, M. Constanza Camargo, Jean Claude Zenklusen, Jay Bowen, Kristen Leraas, Tara M. Lichtenberg, Christina Curtis, Jose A. Seoane, Akinyemi I. Ojesina, David G. Beer, Frank Carey, Ian Forgie, The Cancer Genome Atlas Research Network

Molecular and Clinical Medicine

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Abstract

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.

Original language	English
Pages (from-to)	169-174
Number of pages	6
Journal	Nature
Volume	541
Issue number	7636
Early online date	4 Jan 2017
DOIs	https://doi.org/10.1038/nature20805
Publication status	Published - 12 Jan 2017

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Kim, J., Bowlby, R., Mungall, A. J., Robertson, A. G., Odze, R. D., Cherniack, A. D., Shih, J., Pedamallu, C. S., Cibulskis, C., Dunford, A., Meier, S. R., Kim, J., Raphael, J., Wu, H. T., Wong, A. M., Willis, J. E., Bass, A. J., Derks, S., Garman, K., ... The Cancer Genome Atlas Research Network (2017). Integrated genomic characterization of oesophageal carcinoma. Nature, 541(7636), 169-174. Advance online publication. https://doi.org/10.1038/nature20805

@article{2878b89095aa44f99362d40ceef16cb1,

title = "Integrated genomic characterization of oesophageal carcinoma",

abstract = "Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.",

author = "Jihun Kim and Reanne Bowlby and Mungall, {Andrew J.} and Robertson, {A. Gordon} and Odze, {Robert D.} and Cherniack, {Andrew D.} and Juliann Shih and Pedamallu, {Chandra Sekhar} and Carrie Cibulskis and Andrew Dunford and Meier, {Samuel R.} and Jaegil Kim and J. Raphael and Wu, {Hsin Ta} and Wong, {Alexandra M.} and Willis, {Joseph E.} and Bass, {Adam J.} and Sarah Derks and Katherine Garman and McCall, {Shannon J.} and MacIej Wiznerowicz and Angeliki Pantazi and Michael Parfenov and V{\'e}steinn Thorsson and Ilya Shmulevich and Varsha Dhankani and Michael Miller and Sakai, {Ku Leuven Ryo} and Kenneth Wang and Nikolaus Schultz and Ronglai Shen and Arshi Arora and Nils Weinhold and Francisco S{\'a}nchez-Vega and Kelsen, {David P.} and Julia Zhang and Ina Felau and John Demchok and Rabkin, {Charles S.} and Camargo, {M. Constanza} and Zenklusen, {Jean Claude} and Jay Bowen and Kristen Leraas and Lichtenberg, {Tara M.} and Christina Curtis and Seoane, {Jose A.} and Ojesina, {Akinyemi I.} and Beer, {David G.} and Frank Carey and Ian Forgie and {The Cancer Genome Atlas Research Network}",

note = "This work was supported by the Intramural Research Program and the following grants from the United States National Institutes of Health: 5U24CA143799, 5U24CA143835, 5U24CA143840, 5U24CA143843, 5U24CA143845, 5U24CA143848, 5U24CA143858, 5U24CA143866, 5U24CA143867, 5U24CA143882, 5U24CA143883, 5U24CA144025, U54HG003067, U54HG003079, and U54HG003273, P30CA16672.",

year = "2017",

month = jan,

day = "12",

doi = "10.1038/nature20805",

language = "English",

volume = "541",

pages = "169--174",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7636",

}

Kim, J, Bowlby, R, Mungall, AJ, Robertson, AG, Odze, RD, Cherniack, AD, Shih, J, Pedamallu, CS, Cibulskis, C, Dunford, A, Meier, SR, Kim, J, Raphael, J, Wu, HT, Wong, AM, Willis, JE, Bass, AJ, Derks, S, Garman, K, McCall, SJ, Wiznerowicz, M, Pantazi, A, Parfenov, M, Thorsson, V, Shmulevich, I, Dhankani, V, Miller, M, Sakai, KLR, Wang, K, Schultz, N, Shen, R, Arora, A, Weinhold, N, Sánchez-Vega, F, Kelsen, DP, Zhang, J, Felau, I, Demchok, J, Rabkin, CS, Camargo, MC, Zenklusen, JC, Bowen, J, Leraas, K, Lichtenberg, TM, Curtis, C, Seoane, JA, Ojesina, AI, Beer, DG, Carey, F, Forgie, I & The Cancer Genome Atlas Research Network 2017, 'Integrated genomic characterization of oesophageal carcinoma', Nature, vol. 541, no. 7636, pp. 169-174. https://doi.org/10.1038/nature20805

TY - JOUR

T1 - Integrated genomic characterization of oesophageal carcinoma

AU - Kim, Jihun

AU - Bowlby, Reanne

AU - Mungall, Andrew J.

AU - Robertson, A. Gordon

AU - Odze, Robert D.

AU - Cherniack, Andrew D.

AU - Shih, Juliann

AU - Pedamallu, Chandra Sekhar

AU - Cibulskis, Carrie

AU - Dunford, Andrew

AU - Meier, Samuel R.

AU - Kim, Jaegil

AU - Raphael, J.

AU - Wu, Hsin Ta

AU - Wong, Alexandra M.

AU - Willis, Joseph E.

AU - Bass, Adam J.

AU - Derks, Sarah

AU - Garman, Katherine

AU - McCall, Shannon J.

AU - Wiznerowicz, MacIej

AU - Pantazi, Angeliki

AU - Parfenov, Michael

AU - Thorsson, Vésteinn

AU - Shmulevich, Ilya

AU - Dhankani, Varsha

AU - Miller, Michael

AU - Sakai, Ku Leuven Ryo

AU - Wang, Kenneth

AU - Schultz, Nikolaus

AU - Shen, Ronglai

AU - Arora, Arshi

AU - Weinhold, Nils

AU - Sánchez-Vega, Francisco

AU - Kelsen, David P.

AU - Zhang, Julia

AU - Felau, Ina

AU - Demchok, John

AU - Rabkin, Charles S.

AU - Camargo, M. Constanza

AU - Zenklusen, Jean Claude

AU - Bowen, Jay

AU - Leraas, Kristen

AU - Lichtenberg, Tara M.

AU - Curtis, Christina

AU - Seoane, Jose A.

AU - Ojesina, Akinyemi I.

AU - Beer, David G.

AU - Carey, Frank

AU - Forgie, Ian

AU - The Cancer Genome Atlas Research Network

N1 - This work was supported by the Intramural Research Program and the following grants from the United States National Institutes of Health: 5U24CA143799, 5U24CA143835, 5U24CA143840, 5U24CA143843, 5U24CA143845, 5U24CA143848, 5U24CA143858, 5U24CA143866, 5U24CA143867, 5U24CA143882, 5U24CA143883, 5U24CA144025, U54HG003067, U54HG003079, and U54HG003273, P30CA16672.

PY - 2017/1/12

Y1 - 2017/1/12

N2 - Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.

AB - Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.

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U2 - 10.1038/nature20805

DO - 10.1038/nature20805

M3 - Article

C2 - 28052061

AN - SCOPUS:85016278868

SN - 0028-0836

VL - 541

SP - 169

EP - 174

JO - Nature

JF - Nature

IS - 7636

ER -

Integrated genomic characterization of oesophageal carcinoma

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