Integrated proteomics, phosphoproteomics and metabolomics analyses reveal similarities among giant cell granulomas of the jaws with different genetic mutations.

Abstract

BACKGROUND:

Giant cell granuloma of the jaws are benign osteolytic lesions of the jaws. These lesions are genetically characterized by mutually exclusive somatic mutations at TRPV4, KRAS, and FGFR1, and a fourth molecular subgroup which is wild-type for the three mutations. Irrespective of the molecular background, giant cell granulomas show MAPK/ERK activation. However, it remains unclear if these mutations lead to differences in their molecular signaling in giant cell granulomas.

METHODS:

Metabolomics, proteomics, and phosphoproteomics analyses were carried out in formalin-fixed paraffin-embedded samples of giant cell granuloma of the jaws. The study cohort consisted of five lesions harboring mutations in FGFR1, six in KRAS, five in TRPV4, and five that were wild-type for these mutations.

RESULTS:

Lesions harboring KRAS or FGFR1 mutations showed overall similar proteomics and metabolomics profiles. In all four groups, metabolic pathways showed similarity in apoptosis, cell signaling, gene expression, cell differentiation, and erythrocyte activity. Lesions harboring TRPV4 mutations showed a greater number of enriched pathways related to tissue architecture. On the other hand, the wild-type group presented increased number of enriched pathways related to protein metabolism compared to the other groups.

CONCLUSION:

Despite some minor differences, our results revealed an overall similar molecular profile among the groups with different mutational profile at the metabolic, proteic, and phosphopeptidic levels.

• Authors: Jéssica Gardone Vitório, Filipe Fideles Duarte-Andrade, Thais Dos Santos Fontes Pereira, Marcella Nunes Melo-Braga, Gisele André Baptista Canuto, Adriana Nori de Macedo, Yuri Abner Rocha Lebron, Victor Rezende Moreira, Liza Figueiredo Felicori, Liséte Celina Lange, Lucilaine Valéria de Souza Santos, Martin R Larsen, Carolina Cavalieri Gomes, Ricardo Santiago Gomez
• Journal: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology (J Oral Pathol Med) Vol. 51 Issue 7 Pg. 666-673 (Aug 2022) ISSN: 1600-0714 [Electronic] Denmark
• PMID: 35706152 (Publication Type: Journal Article)
• Copyright: © 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• TRPV Cation Channels
• TRPV4 protein, human
• Proto-Oncogene Proteins p21(ras)

Topics

• Granuloma, Giant Cell (genetics, metabolism)
• Humans
• Jaw (metabolism, pathology)
• Metabolomics
• Mutation
• Proteomics
• Proto-Oncogene Proteins p21(ras) (genetics, metabolism)
• TRPV Cation Channels (genetics, metabolism)