Amplification of chromosomal segment 4q12 in non-small cell lung cancer

Alex H. Ramos; Amit Dutt; Craig Mermel; Sven Perner; Jeonghee Cho; Christopher J. Lafargue; Laura A. Johnson; Ann Cathrin Stiedl; Kumiko E. Tanaka; Adam J. Bass; Jordi Barretina; Barbara A. Weir; Rameen Beroukhim; Roman K. Thomas; John D. Minna; Lucian R. Chirieac; Neal I. Lindeman; Thomas Giordano; David G. Beer; Patrick Wagner; Ignacio I. Wistuba; Mark A. Rubin; Matthew Meyerson

doi:10.4161/cbt.8.21.9764

Amplification of chromosomal segment 4q12 in non-small cell lung cancer

Alex H. Ramos, Amit Dutt, Craig Mermel, Sven Perner, Jeonghee Cho, Christopher J. Lafargue, Laura A. Johnson, Ann Cathrin Stiedl, Kumiko E. Tanaka, Adam J. Bass, Jordi Barretina, Barbara A. Weir, Rameen Beroukhim, Roman K. Thomas, John D. Minna, Lucian R. Chirieac, Neal I. Lindeman, Thomas Giordano, David G. Beer, Patrick WagnerIgnacio I. Wistuba, Mark A. Rubin, Matthew Meyerson^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Institut für Pathologie

87 Zitate (Scopus)

Abstract

In cancer, proto-oncogenes are often altered by genomic amplification. Here we report recurrent focal amplifications of chromosomal segment 4q12 overlapping the proto-oncogenes PDGFRA and KIT in non-small cell lung cancer (NSCscLCc). Ssingle nucleotide polymorphism (SNP) array and fluorescent in situ hybridization (FISH) analysis indicate that 4q12 is amplified in 3-7% of lung adenocarcinomas and 8-10% of lung squamous cell carcinomas. In addition, we demonstrate that the NSCLC cell line NCI-H1703 exhibits focal amplification of PDGFRA and is dependent on PDGFR? activity for cell growth. Treatment of NCI-H1703 cells with PDGFRA-specific shRNAs or with the PDGFR?/KIT small molecule inhibitors imatinib or sunitinib leads to cell growth inhibition. However, these observations do not extend to NSCLC cell lines with lower-amplitude and broader gains of chromosome 4q. Together these observations implicate PDGFRA and KIT as potential oncogenes in NSCLC, but further study is needed to define the specific characteristics of those tumors that could respond to PDGFR?/KIT inhibitors.

Originalsprache	Englisch
Zeitschrift	Cancer Biology and Therapy
Jahrgang	8
Ausgabenummer	21
Seiten (von - bis)	2042-2050
Seitenumfang	9
ISSN	1538-4047
DOIs	https://doi.org/10.4161/cbt.8.21.9764
Publikationsstatus	Veröffentlicht - 01.11.2009

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We thank Shantanu Banerji for critical reading of the manuscript and Christopher A. French for providing microscopy support. A.D. is supported by the Swiss National Science Foundation Fellowship #PBZHB-106297. This work was supported by National Cancer Institute grants 5R01CA109038 and 5P20CA90578 (M.M.).

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10.4161/cbt.8.21.9764

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Ramos, A. H., Dutt, A., Mermel, C., Perner, S., Cho, J., Lafargue, C. J., Johnson, L. A., Stiedl, A. C., Tanaka, K. E., Bass, A. J., Barretina, J., Weir, B. A., Beroukhim, R., Thomas, R. K., Minna, J. D., Chirieac, L. R., Lindeman, N. I., Giordano, T., Beer, D. G., ... Meyerson, M. (2009). Amplification of chromosomal segment 4q12 in non-small cell lung cancer. Cancer Biology and Therapy, 8(21), 2042-2050. https://doi.org/10.4161/cbt.8.21.9764

@article{df71bb6d1e3c40f7a91a7569b0f7d475,

title = "Amplification of chromosomal segment 4q12 in non-small cell lung cancer",

abstract = "In cancer, proto-oncogenes are often altered by genomic amplification. Here we report recurrent focal amplifications of chromosomal segment 4q12 overlapping the proto-oncogenes PDGFRA and KIT in non-small cell lung cancer (NSCscLCc). Ssingle nucleotide polymorphism (SNP) array and fluorescent in situ hybridization (FISH) analysis indicate that 4q12 is amplified in 3-7\% of lung adenocarcinomas and 8-10\% of lung squamous cell carcinomas. In addition, we demonstrate that the NSCLC cell line NCI-H1703 exhibits focal amplification of PDGFRA and is dependent on PDGFR? activity for cell growth. Treatment of NCI-H1703 cells with PDGFRA-specific shRNAs or with the PDGFR?/KIT small molecule inhibitors imatinib or sunitinib leads to cell growth inhibition. However, these observations do not extend to NSCLC cell lines with lower-amplitude and broader gains of chromosome 4q. Together these observations implicate PDGFRA and KIT as potential oncogenes in NSCLC, but further study is needed to define the specific characteristics of those tumors that could respond to PDGFR?/KIT inhibitors.",

author = "Ramos, \{Alex H.\} and Amit Dutt and Craig Mermel and Sven Perner and Jeonghee Cho and Lafargue, \{Christopher J.\} and Johnson, \{Laura A.\} and Stiedl, \{Ann Cathrin\} and Tanaka, \{Kumiko E.\} and Bass, \{Adam J.\} and Jordi Barretina and Weir, \{Barbara A.\} and Rameen Beroukhim and Thomas, \{Roman K.\} and Minna, \{John D.\} and Chirieac, \{Lucian R.\} and Lindeman, \{Neal I.\} and Thomas Giordano and Beer, \{David G.\} and Patrick Wagner and Wistuba, \{Ignacio I.\} and Rubin, \{Mark A.\} and Matthew Meyerson",

note = "Funding Information: We thank Shantanu Banerji for critical reading of the manuscript and Christopher A. French for providing microscopy support. A.D. is supported by the Swiss National Science Foundation Fellowship \#PBZHB-106297. This work was supported by National Cancer Institute grants 5R01CA109038 and 5P20CA90578 (M.M.). Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",

year = "2009",

month = nov,

day = "1",

doi = "10.4161/cbt.8.21.9764",

language = "English",

volume = "8",

pages = "2042--2050",

journal = "Cancer Biology and Therapy",

issn = "1538-4047",

publisher = "Taylor and Francis Ltd.",

number = "21",

}

Ramos, AH, Dutt, A, Mermel, C, Perner, S, Cho, J, Lafargue, CJ, Johnson, LA, Stiedl, AC, Tanaka, KE, Bass, AJ, Barretina, J, Weir, BA, Beroukhim, R, Thomas, RK, Minna, JD, Chirieac, LR, Lindeman, NI, Giordano, T, Beer, DG, Wagner, P, Wistuba, II, Rubin, MA & Meyerson, M 2009, 'Amplification of chromosomal segment 4q12 in non-small cell lung cancer', Cancer Biology and Therapy, Jg. 8, Nr. 21, S. 2042-2050. https://doi.org/10.4161/cbt.8.21.9764

TY - JOUR

T1 - Amplification of chromosomal segment 4q12 in non-small cell lung cancer

AU - Ramos, Alex H.

AU - Dutt, Amit

AU - Mermel, Craig

AU - Perner, Sven

AU - Cho, Jeonghee

AU - Lafargue, Christopher J.

AU - Johnson, Laura A.

AU - Stiedl, Ann Cathrin

AU - Tanaka, Kumiko E.

AU - Bass, Adam J.

AU - Barretina, Jordi

AU - Weir, Barbara A.

AU - Beroukhim, Rameen

AU - Thomas, Roman K.

AU - Minna, John D.

AU - Chirieac, Lucian R.

AU - Lindeman, Neal I.

AU - Giordano, Thomas

AU - Beer, David G.

AU - Wagner, Patrick

AU - Wistuba, Ignacio I.

AU - Rubin, Mark A.

AU - Meyerson, Matthew

N1 - Funding Information: We thank Shantanu Banerji for critical reading of the manuscript and Christopher A. French for providing microscopy support. A.D. is supported by the Swiss National Science Foundation Fellowship #PBZHB-106297. This work was supported by National Cancer Institute grants 5R01CA109038 and 5P20CA90578 (M.M.). Copyright: Copyright 2017 Elsevier B.V., All rights reserved.

PY - 2009/11/1

Y1 - 2009/11/1

N2 - In cancer, proto-oncogenes are often altered by genomic amplification. Here we report recurrent focal amplifications of chromosomal segment 4q12 overlapping the proto-oncogenes PDGFRA and KIT in non-small cell lung cancer (NSCscLCc). Ssingle nucleotide polymorphism (SNP) array and fluorescent in situ hybridization (FISH) analysis indicate that 4q12 is amplified in 3-7% of lung adenocarcinomas and 8-10% of lung squamous cell carcinomas. In addition, we demonstrate that the NSCLC cell line NCI-H1703 exhibits focal amplification of PDGFRA and is dependent on PDGFR? activity for cell growth. Treatment of NCI-H1703 cells with PDGFRA-specific shRNAs or with the PDGFR?/KIT small molecule inhibitors imatinib or sunitinib leads to cell growth inhibition. However, these observations do not extend to NSCLC cell lines with lower-amplitude and broader gains of chromosome 4q. Together these observations implicate PDGFRA and KIT as potential oncogenes in NSCLC, but further study is needed to define the specific characteristics of those tumors that could respond to PDGFR?/KIT inhibitors.

AB - In cancer, proto-oncogenes are often altered by genomic amplification. Here we report recurrent focal amplifications of chromosomal segment 4q12 overlapping the proto-oncogenes PDGFRA and KIT in non-small cell lung cancer (NSCscLCc). Ssingle nucleotide polymorphism (SNP) array and fluorescent in situ hybridization (FISH) analysis indicate that 4q12 is amplified in 3-7% of lung adenocarcinomas and 8-10% of lung squamous cell carcinomas. In addition, we demonstrate that the NSCLC cell line NCI-H1703 exhibits focal amplification of PDGFRA and is dependent on PDGFR? activity for cell growth. Treatment of NCI-H1703 cells with PDGFRA-specific shRNAs or with the PDGFR?/KIT small molecule inhibitors imatinib or sunitinib leads to cell growth inhibition. However, these observations do not extend to NSCLC cell lines with lower-amplitude and broader gains of chromosome 4q. Together these observations implicate PDGFRA and KIT as potential oncogenes in NSCLC, but further study is needed to define the specific characteristics of those tumors that could respond to PDGFR?/KIT inhibitors.

UR - https://www.scopus.com/pages/publications/73549108711

U2 - 10.4161/cbt.8.21.9764

DO - 10.4161/cbt.8.21.9764

M3 - Journal articles

AN - SCOPUS:73549108711

SN - 1538-4047

VL - 8

SP - 2042

EP - 2050

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

IS - 21

ER -

Amplification of chromosomal segment 4q12 in non-small cell lung cancer

Abstract

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