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, 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

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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 languageEnglish
Pages (from-to)169-174
Number of pages6
JournalNature
Volume541
Issue number7636
Early online date4 Jan 2017
DOIs
Publication statusPublished - 12 Jan 2017

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Adenocarcinoma
Carcinoma
Squamous Cell Carcinoma
Neoplasms
Esophageal Neoplasms
Esophagus
Stomach
DNA
Therapeutics
Population
Esophageal Squamous Cell Carcinoma

Cite this

Kim, J., Bowlby, R., Mungall, A. J., Robertson, A. G., Odze, R. D., Cherniack, A. D., ... The Cancer Genome Atlas Research Network (2017). Integrated genomic characterization of oesophageal carcinoma. Nature, 541(7636), 169-174. https://doi.org/10.1038/nature20805
Kim, Jihun ; Bowlby, Reanne ; Mungall, Andrew J. ; Robertson, A. Gordon ; Odze, Robert D. ; Cherniack, Andrew D. ; Shih, Juliann ; Pedamallu, Chandra Sekhar ; Cibulskis, Carrie ; Dunford, Andrew ; Meier, Samuel R. ; Kim, Jaegil ; Raphael, J. ; Wu, Hsin Ta ; Wong, Alexandra M. ; Willis, Joseph E. ; Bass, Adam J. ; Derks, Sarah ; Garman, Katherine ; McCall, Shannon J. ; Wiznerowicz, MacIej ; Pantazi, Angeliki ; Parfenov, Michael ; Thorsson, Vésteinn ; Shmulevich, Ilya ; Dhankani, Varsha ; Miller, Michael ; Sakai, Ku Leuven Ryo ; Wang, Kenneth ; Schultz, Nikolaus ; Shen, Ronglai ; Arora, Arshi ; Weinhold, Nils ; Sánchez-Vega, Francisco ; Kelsen, David P. ; Zhang, Julia ; Felau, Ina ; Demchok, John ; Rabkin, Charles S. ; Camargo, M. Constanza ; Zenklusen, Jean Claude ; Bowen, Jay ; Leraas, Kristen ; Lichtenberg, Tara M. ; Curtis, Christina ; Seoane, Jose A. ; Ojesina, Akinyemi I. ; Beer, David G. ; Carey, Frank ; Forgie, Ian ; The Cancer Genome Atlas Research Network. / Integrated genomic characterization of oesophageal carcinoma. In: Nature. 2017 ; Vol. 541, No. 7636. pp. 169-174.
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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.",
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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

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

In: Nature, Vol. 541, No. 7636, 12.01.2017, p. 169-174.

Research output: Contribution to journalArticle

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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Kim J, Bowlby R, Mungall AJ, Robertson AG, Odze RD, Cherniack AD et al. Integrated genomic characterization of oesophageal carcinoma. Nature. 2017 Jan 12;541(7636):169-174. https://doi.org/10.1038/nature20805