title: Frequent mutation of the major cartilage collagen gene COL2A1 in chondrosarcoma.
abstract: Chondrosarcoma is a heterogeneous collection of malignant bone tumors and is the second most common primary malignancy of bone after osteosarcoma. Recent work has identified frequent, recurrent mutations in IDH1 or IDH2 in nearly half of central chondrosarcomas. However, there has been little systematic genomic analysis of this tumor type, and, thus, the contribution of other genes is unclear. Here we report comprehensive genomic analyses of 49 individuals with chondrosarcoma (cases). We identified hypermutability of the major cartilage collagen gene COL2A1, with insertions, deletions and rearrangements identified in 37% of cases. The patterns of mutation were consistent with selection for variants likely to impair normal collagen biosynthesis. In addition, we identified mutations in IDH1 or IDH2 (59%), TP53 (20%), the RB1 pathway (33%) and Hedgehog signaling (18%).
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Tarpey
authors.forename: Sam
authors.initials: S
authors.lastname: Behjati
authors.forename: Susanna L
authors.initials: SL
authors.lastname: Cooke
authors.forename: Peter
authors.initials: P
authors.lastname: Van Loo
authors.forename: David C
authors.initials: DC
authors.lastname: Wedge
authors.forename: Nischalan
authors.initials: N
authors.lastname: Pillay
authors.forename: John
authors.initials: J
authors.lastname: Marshall
authors.forename: Sarah
authors.initials: S
authors.lastname: O'Meara
authors.forename: Helen
authors.initials: H
authors.lastname: Davies
authors.forename: Serena
authors.initials: S
authors.lastname: Nik-Zainal
authors.forename: David
authors.initials: D
authors.lastname: Beare
authors.forename: Adam
authors.initials: A
authors.lastname: Butler
authors.forename: John
authors.initials: J
authors.lastname: Gamble
authors.forename: Claire
authors.initials: C
authors.lastname: Hardy
authors.forename: Jonathon
authors.initials: J
authors.lastname: Hinton
authors.forename: Ming Ming
authors.initials: MM
authors.lastname: Jia
authors.forename: Alagu
authors.initials: A
authors.lastname: Jayakumar
authors.forename: David
authors.initials: D
authors.lastname: Jones
authors.forename: Calli
authors.initials: C
authors.lastname: Latimer
authors.forename: Mark
authors.initials: M
authors.lastname: Maddison
authors.forename: Sancha
authors.initials: S
authors.lastname: Martin
authors.forename: Stuart
authors.initials: S
authors.lastname: McLaren
authors.forename: Andrew
authors.initials: A
authors.lastname: Menzies
authors.forename: Laura
authors.initials: L
authors.lastname: Mudie
authors.forename: Keiran
authors.initials: K
authors.lastname: Raine
authors.forename: Jon W
authors.initials: JW
authors.lastname: Teague
authors.forename: Jose M C
authors.initials: JM
authors.lastname: Tubio
authors.forename: Dina
authors.initials: D
authors.lastname: Halai
authors.forename: Roberto
authors.initials: R
authors.lastname: Tirabosco
authors.forename: Fernanda
authors.initials: F
authors.lastname: Amary
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Campbell
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Flanagan
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Futreal
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002813:Chondrosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D024043:Collagen Type II / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D056915:DNA Copy Number Variations; D030541:Databases, Genetic; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D060787:Neoplasm Grading; D020641:Polymorphism, Single Nucleotide; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II; D053823:Hedgehog Proteins; D016160:Retinoblastoma Protein