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  • Oncogenomics
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Increased expression and no mutation of the Flap endonuclease (FEN1) gene in human lung cancer

Oncogene volume 22, pages 7243–7246 (2003)Cite this article

Abstract

The underlying molecular mechanisms leading to microsatellite alteration and mutations in human lung cancer remain unknown. Since Flap endonuclease1 (Fen1), which functions in the base excision repair system, has been shown to be involved in tumor progression of mouse models with microsatellite instability in a haplo-insufficient manner, we performed expression and mutation analyses for FEN1 in human lung cancer cell lines. Reverse transcriptase PCR analysis revealed that all 49 lung cancer cell lines (20 small cell lung cancers (SCLCs) and 29 non-small cell lung cancers (NSCLCs)) expressed FEN1. In addition, microarray analysis showed that FEN1 expression was elevated significantly by 1.65-fold (P=0.001) in SCLC cell lines compared to normal lung controls (normal human lung cultures and immortalized normal human bronchial epithelial cell lines). FEN1 protein was abundantly expressed in all 23 lung cancer cell lines (10 SCLCs and 13 NSCLCs) and was expressed at lower levels in three of four normal lung epithelial culture controls. Direct sequencing of genomic DNAs revealed no FEN1 mutation in seven SCLCs and nine NSCLCs. As part of this analysis we discovered and sequenced a FEN1 pseudogene (GenBank accession #AY249897) located at 1p22.2. This pseudogene is amplified from cDNA preparations contaminated with genomic DNA and must be taken into account in any FEN1 mutation analysis studies. Our results suggest that alterations of FEN1 are not likely to contribute to development of lung cancer.

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Abbreviations

SCLC:

small cell lung cancer

NSCLC:

non-small cell lung cancer

HNPCC:

hereditary nonpolyposis colon cancer

RT–PCR:

reverse transcriptase PCR

MSI:

microsatellite instability

MMR, mismatch repair:

BER, base excision repair

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Acknowledgements

This work was supported by Lung Cancer SPORE P50CA70907, and the Gillson Longenbaugh Foundation.

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Authors and Affiliations

  1. Department of Internal Medicine, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, 75390-8593, TX, USA

    Mitsuo Sato, Luc Girard, Ikuo Sekine, Noriaki Sunaga, Ruben D Ramirez, Craig Kamibayashi & John D Minna

  2. Department of Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, 75390-8593, TX, USA

    Mitsuo Sato, Luc Girard, Ikuo Sekine, Noriaki Sunaga, Ruben D Ramirez, Craig Kamibayashi & John D Minna

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  1. Mitsuo Sato
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Correspondence to John D Minna.

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Sato, M., Girard, L., Sekine, I. et al. Increased expression and no mutation of the Flap endonuclease (FEN1) gene in human lung cancer. Oncogene 22, 7243–7246 (2003). https://doi.org/10.1038/sj.onc.1206977

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