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

Marcus Kind1, Jolanta Klukowska-Rötzler1,2, Sabina Berezowska3

  • 1University Children's Hospital Bern, Freiburgstrasse 31, Bern, Switzerland.

Plos One
|November 1, 2017
PubMed

Insights

This study investigated PIK3C2B mutations in non-small cell lung cancer with squamous cell carcinoma (NSCLC-SQCC). Researchers found no evidence that PIK3C2B alterations contribute to NSCLC-SQCC development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Phosphoinositide 3-kinase (PI3K) signaling is frequently altered in non-small cell lung cancer with squamous cell carcinoma (NSCLC-SQCC).
  • While PI3K pathway components are established drivers of SQCC, the oncogenic role of PIK3C2B alterations remains unclear.

Purpose of the Study:

  • To investigate the potential oncogenic role of PIK3C2B mutations in NSCLC-SQCC.
  • To functionally assess specific PIK3C2B kinase domain mutations.

Main Methods:

  • Sanger sequencing of a cohort of 362 NSCLC-SQCC tumors for four reported PIK3C2B somatic mutations.
  • Functional analysis of two PIK3C2B mutations (C1181, H1208R) affecting the kinase domain.
  • Analysis of PIK3C2B alterations in NSCLC-SQCC tumors from The Cancer Genome Atlas (TCGA).

Main Results:

  • None of the screened PIK3C2B mutations were detected in the NSCLC-SQCC cohort.
  • Known hotspot PIK3CA mutations were found at expected frequencies.
  • PIK3C2B kinase domain mutations did not alter downstream signaling pathways.
  • TCGA data further supported a lack of oncogenic potential for PIK3C2B kinase domain mutations.

Conclusions:

  • PIK3C2B alterations appear to play a minimal role in the oncogenesis of NSCLC-SQCC.
  • Further research may be needed to fully elucidate the function of PIK3C2B in lung cancer, but current evidence suggests limited involvement in SQCC.

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