Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer

  • Authors:
    • Nayoung Kim
    • Mee Song
    • Somin Kim
    • Yujeong Seo
    • Yonghwan Kim
    • Sukjoon Yoon
  • View Affiliations

  • Published online on: November 20, 2015     https://doi.org/10.3892/ijo.2015.3262
  • Pages: 367-375
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Abstract

Genetic alterations in lung cancer are distinctly represented in non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). Mutation of the RB1 and CDKN2A genes, which are tightly associated with cell cycle regulation, is exclusive to SCLC and NSCLC cells, respectively. Through the systematic analysis of transcriptome and proteome datasets for 318 cancer cell lines, we characterized differential gene expression and protein regulation in RB1-mutant SCLC and CDKN2A-mutant NSCLC. Many of the genes and proteins associated with RB1-mutant SCLC cell lines belong to functional categories of gene expression and transcription, whereas those associated with CDKN2A-mutant NSCLC cell lines were enriched in gene sets of the extracellular matrix and focal adhesion. These results indicate that the loss of RB1 and CDKN2A function induces distinctively different signaling cascades in SCLC and NSCLC cells. In addition, knockdown of the RB1 gene in CKDN2A-mutant cell lines (and vice versa) synergistically inhibits cancer cell proliferation. The present study on the exclusive role of RB1 and CDKN2A mutations in lung cancer subtypes demonstrates a synthetic lethal strategy for cancer regulation.
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January-2016
Volume 48 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kim N, Song M, Kim S, Seo Y, Kim Y and Yoon S: Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer. Int J Oncol 48: 367-375, 2016
APA
Kim, N., Song, M., Kim, S., Seo, Y., Kim, Y., & Yoon, S. (2016). Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer. International Journal of Oncology, 48, 367-375. https://doi.org/10.3892/ijo.2015.3262
MLA
Kim, N., Song, M., Kim, S., Seo, Y., Kim, Y., Yoon, S."Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer". International Journal of Oncology 48.1 (2016): 367-375.
Chicago
Kim, N., Song, M., Kim, S., Seo, Y., Kim, Y., Yoon, S."Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer". International Journal of Oncology 48, no. 1 (2016): 367-375. https://doi.org/10.3892/ijo.2015.3262