title: Isocitrate dehydrogenase 1 mutations (IDH1) and p16/CDKN2A copy number change in conventional chondrosarcomas.
abstract: To determine whether IDH1 mutations are present in primary and relapsed (local and distal) conventional central chondrosarcomas; and secondly, to assess if loss of p16/CDKN2A is associated with tumour grade progression, 102 tumour samples from 37 patients, including material from presenting and relapse events, were assessed. All wild-type cases for IDH1 R132 substitutions were also tested for IDH2 R172 and R140 alterations. The primary tumour and the most recent relapse sample were tested for p16/CDKN2A by interphase fluorescence in situ hybridisation. An additional 120 central cartilaginous tumours from different patients were also tested for p16/CDKN2A copy number. The study shows that if an IDH1 mutation were detected in a primary central chondrosarcoma, it is always detected at the time of presentation, and the same mutation is detected in local recurrences and metastatic events. We show that p16/CDKN2A copy number variation occurs subsequent to the IDH1 mutation, and confirm that p16/CDKN2A copy number variation occurs in 75% of high grade central chondrosarcomas, and not in low grade cartilaginous tumours. Finally, p16/CDKN2A copy number variation is seen in both the IDH1 wild-type and mutant cartilaginous central tumours.
authors.affiliation: Cancer Institute, University College London, Huntley Street, WC1E 6BT, London, UK, fernanda.amary@nhs.net.
authors.forename: M Fernanda
authors.initials: MF
authors.lastname: Amary
authors.forename: Hongtao
authors.initials: H
authors.lastname: Ye
authors.forename: Georgina
authors.initials: G
authors.lastname: Forbes
authors.forename: Stephen
authors.initials: S
authors.lastname: Damato
authors.forename: Francesca
authors.initials: F
authors.lastname: Maggiani
authors.forename: Robin
authors.initials: R
authors.lastname: Pollock
authors.forename: Roberto
authors.initials: R
authors.lastname: Tirabosco
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Flanagan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000235:genetics*; D002813:Chondrosarcoma / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D019942:Genes, p16; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human