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Direct evidence for the age-dependent demise of GNAS-mutated cells in oral fibrous dysplasia
- Source :
- Archives of Oral Biology. 93:133-140
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Objective Fibrous dysplasia (FD) is a benign bone disease characterized by fibro-osseous lesions. FD is caused by somatic mutations in the gene, guanine nucleotide-binding protein, alpha stimulating activity polypeptide 1 (GNAS), which encodes the G protein subunit, GsĪ±. FD manifests early in life, but the growth of lesions usually ceases in adulthood. FD lesions often exhibit somatic mutation mosaicism. In this study, the relationship between lesion growth and mutation prevalence within a lesion was investigated. Design Lesions from five FD patients were characterized by radiographical, histological and immunohistochemical methods. To accurately calculate the prevalence of mutations within lesions, GNAS codon 201 in genomic DNA isolated from fresh surgical FD specimens was sequenced. Results Uniquely, a lesion in one 46-year-old patient was still growing, enabling simultaneous analysis of both stable-old and active-new FD lesions in the same patient. Immunohistochemical analysis indicated that a newer, proximal lesion was growing while an older, distal lesion was not. The mutation prevalence differed between these lesions; it was low in the old and high in the new lesion. Thus, the frequency of mutated cells had decreased in the older lesion. Conclusions This is the first direct evidence for the age-dependent demise of mutated cells in FD, helping to explain why FD lesion growth generally ceases in adulthood.
- Subjects :
- Adult
Male
Reoperation
Pathology
medicine.medical_specialty
Bone disease
Somatic cell
DNA Mutational Analysis
medicine.disease_cause
Lesion
03 medical and health sciences
0302 clinical medicine
Germline mutation
Radiography, Panoramic
Chromogranins
GTP-Binding Protein alpha Subunits, Gs
medicine
GNAS complex locus
Humans
Mandibular Diseases
General Dentistry
Mutation
biology
business.industry
Fibrous dysplasia
Age Factors
Fibrous Dysplasia of Bone
030206 dentistry
Cell Biology
General Medicine
medicine.disease
Immunohistochemistry
Otorhinolaryngology
030220 oncology & carcinogenesis
biology.protein
Female
medicine.symptom
business
Subjects
Details
- ISSN :
- 00039969
- Volume :
- 93
- Database :
- OpenAIRE
- Journal :
- Archives of Oral Biology
- Accession number :
- edsair.doi.dedup.....e90590ed2a0fe45ec5986bfd3edf6a37