KRAS mutations in implant‐associated peripheral giant cell granulomaShow others and affiliations
2020 (English)In: Oral Diseases, ISSN 1354-523X, E-ISSN 1601-0825, Vol. 26, no 2, p. 334-340Article in journal (Refereed) Published
Abstract [en]
Objectives: To investigate the molecular pathogenesis of implant‐associated peripheral giant cell granuloma (IA‐PGCG). Methods: A convenience sample of 15 IA‐PGCG cases was selected. Hotspot mutations of KRAS, FGFR1, and TRPV4 genes, previously reported in conventional giant cell lesions of the jaws, were investigated by Sanger sequencing. As these mutations could activate MAPK/ERK pathway, the expression of phospho‐ERK1/2 was also evaluated by immunohistochemistry. Results: KRAS mutations were detected in 8/15 (53.4%) samples. Similar to conventional peripheral giant cell granuloma, the KRAS mutations most frequently occurred in codon 146 (p.A146V, n = 3), followed by codon 12 (p.G12A and p.G12D, n = 1 each) and codon 14 (p.V14L, n = 1). Variants of unknown significance (VUS) were also detected in two cases, affecting codons 37 (p.E37K) and 127 (p.T127I). All samples showed wild‐type (WT) sequences for FGFR1 and TRPV4 genes. Consistent with MAPK/ERK pathway activation, all mononuclear cells of the lesion showed strong staining for phospho‐ERK1/2 protein in the immunohistochemical analysis. Conclusions: KRAS mutations and activation of the MAPK‐ERK signaling pathway occur in IA‐PGCG. This is the first study to demonstrate cancer‐associated gene mutations in a non‐neoplastic reactive condition associated with dental implants.
Place, publisher, year, edition, pages
John Wiley & Sons, 2020. Vol. 26, no 2, p. 334-340
Keywords [en]
Giant cell granuloma, Dental implants, MAPK, RAS, Somatic mutations, Benign inflammatory lesions
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:mau:diva-5678DOI: 10.1111/odi.13241ISI: 000503345200001PubMedID: 31758745Scopus ID: 2-s2.0-85076759556Local ID: 30469OAI: oai:DiVA.org:mau-5678DiVA, id: diva2:1402547
2020-02-282020-02-282024-03-27Bibliographically approved