SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

Adam J. Bass; Hideo Watanabe; Craig H. Mermel; Soyoung Yu; Sven Perner; Roel G. Verhaak; So Young Kim; Leslie Wardwell; Pablo Tamayo; Irit Gat-Viks; Alex H. Ramos; Michele S. Woo; Barbara A. Weir; Gad Getz; Rameen Beroukhim; Michael O'Kelly; Amit Dutt; Orit Rozenblatt-Rosen; Piotr Dziunycz; Justin Komisarof; Lucian R. Chirieac; Christopher J. Lafargue; Veit Scheble; Theresia Wilbertz; Changqing Ma; Shilpa Rao; Hiroshi Nakagawa; Douglas B. Stairs; Lin Lin; Thomas J. Giordano; Patrick Wagner; John D. Minna; Adi F. Gazdar; Chang Qi Zhu; Marcia S. Brose; Ivan Cecconello; Ulysses Ribeiro; Suely K. Marie; Olav Dahl; Ramesh A. Shivdasani; Ming Sound Tsao; Mark A. Rubin; Kwok K. Wong; Aviv Regev; William C. Hahn; David G. Beer; Anil K. Rustgi; Matthew Meyerson

doi:10.1038/ng.465

SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

Adam J. Bass, Hideo Watanabe, Craig H. Mermel, Soyoung Yu, Sven Perner, Roel G. Verhaak, So Young Kim, Leslie Wardwell, Pablo Tamayo, Irit Gat-Viks, Alex H. Ramos, Michele S. Woo, Barbara A. Weir, Gad Getz, Rameen Beroukhim, Michael O'Kelly, Amit Dutt, Orit Rozenblatt-Rosen, Piotr Dziunycz, Justin KomisarofLucian R. Chirieac, Christopher J. Lafargue, Veit Scheble, Theresia Wilbertz, Changqing Ma, Shilpa Rao, Hiroshi Nakagawa, Douglas B. Stairs, Lin Lin, Thomas J. Giordano, Patrick Wagner, John D. Minna, Adi F. Gazdar, Chang Qi Zhu, Marcia S. Brose, Ivan Cecconello, Ulysses Ribeiro, Suely K. Marie, Olav Dahl, Ramesh A. Shivdasani, Ming Sound Tsao, Mark A. Rubin, Kwok K. Wong, Aviv Regev, William C. Hahn, David G. Beer, Anil K. Rustgi, Matthew Meyerson

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Abstract

Lineage-survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development. Here we show that a peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas (SCCs) of the lung and esophagus contains the transcription factor gene SOX2, which is mutated in hereditary human esophageal malformations, is necessary for normal esophageal squamous development, promotes differentiation and proliferation of basal tracheal cells and cooperates in induction of pluripotent stem cells. SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 here cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC.

Original language	English (US)
Pages (from-to)	1238-1242
Number of pages	5
Journal	Nature genetics
Volume	41
Issue number	11
DOIs	https://doi.org/10.1038/ng.465
State	Published - Nov 2009

ASJC Scopus subject areas

Genetics

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Bass, A. J., Watanabe, H., Mermel, C. H., Yu, S., Perner, S., Verhaak, R. G., Kim, S. Y., Wardwell, L., Tamayo, P., Gat-Viks, I., Ramos, A. H., Woo, M. S., Weir, B. A., Getz, G., Beroukhim, R., O'Kelly, M., Dutt, A., Rozenblatt-Rosen, O., Dziunycz, P., ... Meyerson, M. (2009). SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nature genetics, 41(11), 1238-1242. https://doi.org/10.1038/ng.465

Bass, AJ, Watanabe, H, Mermel, CH, Yu, S, Perner, S, Verhaak, RG, Kim, SY, Wardwell, L, Tamayo, P, Gat-Viks, I, Ramos, AH, Woo, MS, Weir, BA, Getz, G, Beroukhim, R, O'Kelly, M, Dutt, A, Rozenblatt-Rosen, O, Dziunycz, P, Komisarof, J, Chirieac, LR, Lafargue, CJ, Scheble, V, Wilbertz, T, Ma, C, Rao, S, Nakagawa, H, Stairs, DB, Lin, L, Giordano, TJ, Wagner, P, Minna, JD, Gazdar, AF, Zhu, CQ, Brose, MS, Cecconello, I, Ribeiro, U, Marie, SK, Dahl, O, Shivdasani, RA, Tsao, MS, Rubin, MA, Wong, KK, Regev, A, Hahn, WC, Beer, DG, Rustgi, AK & Meyerson, M 2009, 'SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas', Nature genetics, vol. 41, no. 11, pp. 1238-1242. https://doi.org/10.1038/ng.465

@article{832716d46cba4726a96b9e4a9bfc2d34,

title = "SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas",

abstract = "Lineage-survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development. Here we show that a peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas (SCCs) of the lung and esophagus contains the transcription factor gene SOX2, which is mutated in hereditary human esophageal malformations, is necessary for normal esophageal squamous development, promotes differentiation and proliferation of basal tracheal cells and cooperates in induction of pluripotent stem cells. SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 here cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC.",

author = "Bass, {Adam J.} and Hideo Watanabe and Mermel, {Craig H.} and Soyoung Yu and Sven Perner and Verhaak, {Roel G.} and Kim, {So Young} and Leslie Wardwell and Pablo Tamayo and Irit Gat-Viks and Ramos, {Alex H.} and Woo, {Michele S.} and Weir, {Barbara A.} and Gad Getz and Rameen Beroukhim and Michael O'Kelly and Amit Dutt and Orit Rozenblatt-Rosen and Piotr Dziunycz and Justin Komisarof and Chirieac, {Lucian R.} and Lafargue, {Christopher J.} and Veit Scheble and Theresia Wilbertz and Changqing Ma and Shilpa Rao and Hiroshi Nakagawa and Stairs, {Douglas B.} and Lin Lin and Giordano, {Thomas J.} and Patrick Wagner and Minna, {John D.} and Gazdar, {Adi F.} and Zhu, {Chang Qi} and Brose, {Marcia S.} and Ivan Cecconello and Ulysses Ribeiro and Marie, {Suely K.} and Olav Dahl and Shivdasani, {Ramesh A.} and Tsao, {Ming Sound} and Rubin, {Mark A.} and Wong, {Kwok K.} and Aviv Regev and Hahn, {William C.} and Beer, {David G.} and Rustgi, {Anil K.} and Matthew Meyerson",

note = "Funding Information: We thank J. Francis, J. Cho, A. Schinzel, R. Firestein, I. Guney and J. Boehm for technical advice and discussions. A.J.B. is supported by the Harvard Clinical Investigator Training Program and American Society of Clinical Oncology. H.W. is supported by a Ruth L. Kirschstein NRSA T32 institutional training grant. R.G.V. is supported by the KWF Kankerbestrijding. The Morphology, Molecular Biology and Cell Culture Core of 5P01CA098101-05 (A.K.R.) provided tissue processing for this project. This work was supported by US Department of Defense VITAL grant (J.D.M, A.F.G.) and by National Cancer Institute grants K08CA134931 (A.J.B.), P50CA70907 (J.D.M, A.F.G.), R33CA128625 (W.C.H.), R01CA071606-12 (D.G.B.), P01CA098101-05 (A.K.R.) and R01CA109038 and P50CA90578 (M.M.). Funding for lung SCC SNP arrays was provided by Genentech, Inc. Funding was provided by the Sara Thomas Monopoli Lung Cancer Research Fund and the Seaman Corporation Fund for Lung Cancer Research.",

year = "2009",

month = nov,

doi = "10.1038/ng.465",

language = "English (US)",

volume = "41",

pages = "1238--1242",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "11",

}

TY - JOUR

T1 - SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

AU - Bass, Adam J.

AU - Watanabe, Hideo

AU - Mermel, Craig H.

AU - Yu, Soyoung

AU - Perner, Sven

AU - Verhaak, Roel G.

AU - Kim, So Young

AU - Wardwell, Leslie

AU - Tamayo, Pablo

AU - Gat-Viks, Irit

AU - Ramos, Alex H.

AU - Woo, Michele S.

AU - Weir, Barbara A.

AU - Getz, Gad

AU - Beroukhim, Rameen

AU - O'Kelly, Michael

AU - Dutt, Amit

AU - Rozenblatt-Rosen, Orit

AU - Dziunycz, Piotr

AU - Komisarof, Justin

AU - Chirieac, Lucian R.

AU - Lafargue, Christopher J.

AU - Scheble, Veit

AU - Wilbertz, Theresia

AU - Ma, Changqing

AU - Rao, Shilpa

AU - Nakagawa, Hiroshi

AU - Stairs, Douglas B.

AU - Lin, Lin

AU - Giordano, Thomas J.

AU - Wagner, Patrick

AU - Minna, John D.

AU - Gazdar, Adi F.

AU - Zhu, Chang Qi

AU - Brose, Marcia S.

AU - Cecconello, Ivan

AU - Ribeiro, Ulysses

AU - Marie, Suely K.

AU - Dahl, Olav

AU - Shivdasani, Ramesh A.

AU - Tsao, Ming Sound

AU - Rubin, Mark A.

AU - Wong, Kwok K.

AU - Regev, Aviv

AU - Hahn, William C.

AU - Beer, David G.

AU - Rustgi, Anil K.

AU - Meyerson, Matthew

N1 - Funding Information: We thank J. Francis, J. Cho, A. Schinzel, R. Firestein, I. Guney and J. Boehm for technical advice and discussions. A.J.B. is supported by the Harvard Clinical Investigator Training Program and American Society of Clinical Oncology. H.W. is supported by a Ruth L. Kirschstein NRSA T32 institutional training grant. R.G.V. is supported by the KWF Kankerbestrijding. The Morphology, Molecular Biology and Cell Culture Core of 5P01CA098101-05 (A.K.R.) provided tissue processing for this project. This work was supported by US Department of Defense VITAL grant (J.D.M, A.F.G.) and by National Cancer Institute grants K08CA134931 (A.J.B.), P50CA70907 (J.D.M, A.F.G.), R33CA128625 (W.C.H.), R01CA071606-12 (D.G.B.), P01CA098101-05 (A.K.R.) and R01CA109038 and P50CA90578 (M.M.). Funding for lung SCC SNP arrays was provided by Genentech, Inc. Funding was provided by the Sara Thomas Monopoli Lung Cancer Research Fund and the Seaman Corporation Fund for Lung Cancer Research.

PY - 2009/11

Y1 - 2009/11

N2 - Lineage-survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development. Here we show that a peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas (SCCs) of the lung and esophagus contains the transcription factor gene SOX2, which is mutated in hereditary human esophageal malformations, is necessary for normal esophageal squamous development, promotes differentiation and proliferation of basal tracheal cells and cooperates in induction of pluripotent stem cells. SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 here cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC.

AB - Lineage-survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development. Here we show that a peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas (SCCs) of the lung and esophagus contains the transcription factor gene SOX2, which is mutated in hereditary human esophageal malformations, is necessary for normal esophageal squamous development, promotes differentiation and proliferation of basal tracheal cells and cooperates in induction of pluripotent stem cells. SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 here cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC.

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EP - 1242

JO - Nature genetics

JF - Nature genetics

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ER -

SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

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