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Cellular Oncology

, Volume 41, Issue 4, pp 395–408 | Cite as

Identification of subsets of actionable genetic alterations in KRAS-mutant lung cancers using association rule mining

  • Junior Tayou
Original Paper

Abstract

Background

Lung cancer is the leading cause of cancer-related death in both men and women. KRAS mutations occur in ~ 25% of patients with lung cancer, and the presence of these mutations is associated with a poor prognosis. Unfortunately, efforts to directly target KRAS or its associated downstream MAPK or PI3K/AKT/mTOR pathways have seen little or no benefits. Here, I hypothesize that KRAS-mutant tumors do not respond to KRAS pathway therapies due to the co-occurrence of other activated cell survival pathways and/or mechanisms.

Methods and results

To identify other potentially activated cell survival pathways in KRAS-mutant tumors, I performed association rule mining on somatic mutations in 725 metastatic lung cancer patient samples. I identified 67 additional genes that were mutated in at least 10% of the samples with KRAS mutations. This gene list was enriched with genes involved in the MAPK, AKT and STAT3 pathways, as well as in cell-cell adhesion, DNA repair, chromatin remodeling and the Wnt/β-catenin pathway. I also identified 160 overlapping subsets of three or more genes that code for oncogenic or tumor suppressive proteins that were mutated in at least 10% of the KRAS-mutant tumors.

Conclusions

I identified several genes that are co-mutated in primary KRAS-mutant lung cancer samples. I also identified subpopulations of KRAS-mutant lung cancers based on sets of genes that were co-mutated. Pre-clinical models that capture these subsets of KRAS-mutant tumors may enhance our understanding of lung cancer development and, in addition, facilitate the design of personalized treatment strategies for lung cancer patients carrying KRAS mutations.

Keywords

Metastatic lung cancer KRAS Genetic mutations Unsupervised machine learning Association rule mining 

Notes

Acknowledgements

I thank Michael Birnbaum (University of Miami) for careful reading of the manuscript and excellent suggestions.

Compliance with ethical standards

Ethics approval and consent of participants

Not applicable.

Consent for publication

Not applicable.

Competing interests

None declared.

Supplementary material

13402_2018_377_MOESM1_ESM.csv (385 kb)
ESM 1 (CSV 384 kb)
13402_2018_377_MOESM2_ESM.csv (8 kb)
ESM 2 (CSV 7 kb)
13402_2018_377_MOESM3_ESM.csv (14 kb)
ESM 3 (CSV 13 kb)

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Copyright information

© International Society for Cellular Oncology 2018

Authors and Affiliations

  • Junior Tayou
    • 1
  1. 1.AustinUSA

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