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

Autor: Vitório JG; Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil., Duarte-Andrade FF; Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil., Pereira TDSF; Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil., Melo-Braga MN; Department of Biochemistry and Immunology, Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil., Canuto GAB; Department of Analytical Chemistry, Institute of Chemistry, Universidade Federal da Bahia (UFBA), Salvador, Brazil., Macedo AN; Department of Analytical Chemistry, Institute of Chemistry, Universidade Federal da Minas Gerais (UFMG), Belo Horizonte, Brazil., Lebron YAR; Department of Sanitary and Environmental Engineering, Engineer School, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil., Moreira VR; Department of Sanitary and Environmental Engineering, Engineer School, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil., Felicori LF; Department of Biochemistry and Immunology, Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil., Lange LC; Department of Sanitary and Environmental Engineering, Engineer School, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil., Santos LVS; Department of Sanitary and Environmental Engineering, Engineer School, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil., Larsen MR; Department of Biochemistry and Molecular Biology, University of Southern Denmark (SDU), Odense, Denmark., Gomes CC; Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil., Gomez RS; Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
Jazyk: angličtina
Zdroj: 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] 2022 Aug; Vol. 51 (7), pp. 666-673. Date of Electronic Publication: 2022 Jul 11.
DOI: 10.1111/jop.13327
Abstrakt: 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.
(© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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