title: Evidence of somatic mutations in osteoarthritis.
abstract: We examined, cytogenetically and by in situ hybridization (ISH) techniques, the synovia, osteophytes, and articular cartilage from 32 patients with pronounced osteoarthritis (OA), a prevalent form of arthropathy characterized by progressive reduction of articular cartilage, and synovial samples from 17 control patients. In short-term cultures, clonal chromosome aberrations, in particular the gain of chromosomes 7 (+7) and 5 (+5), were found to be strongly associated with OA. These aberrations were found in almost 90% of the cultures from synovia and osteophytes, whereas only 1/11 synovial samples from joints unequivocally unaffected by OA had cells with +5 or +7. The in vivo nature of trisomy 7 was demonstrated by ISH on uncultured cells, and serial passaging showed that cells with +7 had a proliferative advantage in vitro. Thus, the combined data indicate that cells with somatic mutations appear early and may be influential in the disease process leading to OA.
authors.affiliation: Department of Clinical Genetics, University Hospital, Lund, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Mertens
authors.forename: E
authors.initials: E
authors.lastname: Pålsson
authors.forename: A
authors.initials: A
authors.lastname: Lindstrand
authors.forename: S
authors.initials: S
authors.lastname: Toksvig-Larsen
authors.forename: S
authors.initials: S
authors.lastname: Knuutila
authors.forename: M L
authors.initials: ML
authors.lastname: Larramendy
authors.forename: W
authors.initials: W
authors.lastname: el-Rifai
authors.forename: J
authors.initials: J
authors.lastname: Limon
authors.forename: F
authors.initials: F
authors.lastname: Mitelman
authors.forename: N
authors.initials: N
authors.lastname: Mandahl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D002897:Chromosomes, Human, Pair 7; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics*; D013583:Synovial Membrane / Q000737:chemistry; D014314:Trisomy