Tumor Biology

, Volume 36, Issue 11, pp 8773–8780 | Cite as

Association of CCND1 overexpression with KRAS and PTEN alterations in specific subtypes of non-small cell lung carcinoma and its influence on patients’ outcome

  • Miodrag Dragoj
  • Zorica Milosevic
  • Jasna Bankovic
  • Jelena Dinic
  • Milica Pesic
  • Nikola Tanic
  • Tijana Stankovic
Research Article


Cyclin D1 is one of the major cellular oncogenes, overexpressed in number of human cancers, including non-small cell lung carcinoma (NSCLC). However, it does not exert tumorigenic activity by itself, but rather cooperates with other altered oncogenes and tumor suppressors. Therefore, in the present study, we have examined mutual role of cyclin D1, KRAS, and PTEN alterations in the pathogenesis of NSCLC and their potential to serve as multiple molecular markers for this disease. CCND1 gene amplification and gene expression were analyzed in relation to mutational status of KRAS gene as well as to PTEN alterations (loss of heterozygosity and promoter hypermethylation) in NSCLC patient samples. Moreover, the effect of these co-alterations on patient survival was examined. Amplified CCND1 gene was exclusively associated with increased gene expression. Statistical analyses also revealed significant association between CCND1 overexpression and KRAS mutations in the whole group and in the groups of patients with adenocarcinoma, grade 1/2, and stage I/II. In addition, CCND1 overexpression was significantly related to PTEN promoter hypermethylation in the whole group and in the group of patients with squamous cell carcinoma and lymph node invasion. These joint alterations also significantly shortened patients’ survival and were shown to be an independent factor for adverse prognosis. Overall results point that cyclin D1 expression cooperates with KRAS and PTEN alterations in pathogenesis of NSCLC, and they could serve as potential multiple molecular markers for specific subgroups of NSCLC patients as well as prognostic markers for this type of cancer.


CCND1 KRAS PTEN Non-small cell lung carcinoma 



This study was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (grant No III41031).

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Miodrag Dragoj
    • 1
  • Zorica Milosevic
    • 1
  • Jasna Bankovic
    • 1
  • Jelena Dinic
    • 1
  • Milica Pesic
    • 1
  • Nikola Tanic
    • 1
  • Tijana Stankovic
    • 1
  1. 1.Department of NeurobiologyUniversity of Belgrade, Institute for Biological ResearchBelgradeSerbia

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