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

Research output: Contribution to journal › Article › peer-review

82 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2042-2050
Number of pages	9
Journal	Cancer Biology and Therapy
Volume	8
Issue number	21
DOIs	https://doi.org/10.4161/cbt.8.21.9764
State	Published - Nov 1 2009

Keywords

4q12
Amplification
Imatinib
KIT
Lung cancer
NSCLC
PDGFRA
Sunitinib

ASJC Scopus subject areas

Molecular Medicine
Oncology
Pharmacology
Cancer Research

Access to Document

10.4161/cbt.8.21.9764

Cite this

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

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, vol. 8, no. 21, pp. 2042-2050. https://doi.org/10.4161/cbt.8.21.9764

@article{a311e05902044c5ca5db0d739bdfdfd3,

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.",

keywords = "4q12, Amplification, Imatinib, KIT, Lung cancer, NSCLC, PDGFRA, Sunitinib",

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.).",

year = "2009",

month = nov,

day = "1",

doi = "10.4161/cbt.8.21.9764",

language = "English (US)",

volume = "8",

pages = "2042--2050",

journal = "Cancer Biology and Therapy",

issn = "1538-4047",

publisher = "Landes Bioscience",

number = "21",

}

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.).

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.

KW - 4q12

KW - Amplification

KW - Imatinib

KW - KIT

KW - Lung cancer

KW - NSCLC

KW - PDGFRA

KW - Sunitinib

UR - http://www.scopus.com/inward/record.url?scp=73549108711&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73549108711&partnerID=8YFLogxK

U2 - 10.4161/cbt.8.21.9764

DO - 10.4161/cbt.8.21.9764

M3 - Article

C2 - 19755855

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

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this