Questioning the role of selected somatic PIK3C2B mutations in squamous non-small cell lung cancer oncogenesis

PLoS One. 2017 Oct 31;12(10):e0187308. doi: 10.1371/journal.pone.0187308. eCollection 2017.

Abstract

PI3K signaling is frequently dysregulated in NSCLC-SQCC. In contrast to well characterized components of the PI3K signaling network contributing to the formation of SQCC, potential oncogenic effects of alterations in PIK3C2B are poorly understood. Here, a large cohort (n = 362) of NSCLC-SQCC was selectively screened for four reported somatic mutations in PIK3C2B via Sanger sequencing. In addition, two mutations leading to an amino acid exchange in the kinase domain (C1181, H1208R) were examined on a functional level. None of the mutations were identified in the cohort while well characterized hotspot PIK3CA mutations were observed at the expected frequency. Ultimately, kinase domain mutations in PI3KC2β were found to have no altering effect on downstream signaling. A set of SQCC tumors sequenced by The Cancer Genome Atlas (TCGA) equally indicates a lack of oncogenic potential of the kinase domain mutations or PIK3C2B in general. Taken together, this study suggests that PIK3C2B might only have a minor role in SQCC oncogenesis.

Publication types

  • Validation Study

MeSH terms

  • Carcinogenesis
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Class II Phosphatidylinositol 3-Kinases / genetics*
  • Cohort Studies
  • HEK293 Cells
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mutation*

Substances

  • Class II Phosphatidylinositol 3-Kinases
  • PIK3C2B protein, human

Grants and funding

This work was supported by the Swiss National Science Foundation grant (146464). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.