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.
Highlights
Phosphoinositide-3-kinases (PI3Ks) are able to phosphorylate the inositol ring of three different phosphatidylinositol lipid substrates (PtdIns, PtdIns4P, PtdIns(4,5)P2), minor compounds on the cytosolic site of eukaryotic cell membranes
A large cohort of non-small cell lung cancer (NSCLC)-squamous cell carcinoma (SQCC) tumors was screened for four reported PIK3C2B missense mutations leading to amino acid exchanges (P117A, C1181F, H1208R, L1469F) [20]
Kinase domain mutations C1181F and H1208R were assessed on a functional level
Summary
Phosphoinositide-3-kinases (PI3Ks) are able to phosphorylate the inositol ring of three different phosphatidylinositol lipid substrates (PtdIns, PtdIns4P, PtdIns(4,5)P2), minor compounds on the cytosolic site of eukaryotic cell membranes. Following activation by upstream agonists such as receptor tyrosine kinases (RTKs) or G protein coupled receptors (GPCR), PI3Ks generate 3-phosphoinositides as second messengers. These 3-phosphinositides coordinate the function and localization of numerous effector proteins. Eight different catalytic PI3K isoforms have been described that are subdivided into three different classes (class I, class II and class III). This classification is based on substrate specificity, associated co-factors and sequence homologies
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
