Osteosarcoma_Whole_Genome - EGA European Genome-Phenome Archive

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Dataset ID	Description	Technology	Samples
EGAD00001000147	Osteosarcoma Whole Genome	Illumina HiSeq 2000	108
EGAD00001000646	A selection of human cancers harbours somatic driver mutations in genes encoding histones, most notably childhood brain tumours with K27M substitutions of the histone 3.3 gene, H3F3A. We performed whole genome sequencing of the benign cartilage tumour, chondroblastoma, and targeted sequencing of histone 3.3 genes, H3F3A and H3F3B, in seven further skeletal tumour types. We identified an exceptionally high prevalence of novel histone 3.3 driver mutations at glycine 34 and at lysine 36. Histone 3.3 gene mutations were found in 91% in giant cell tumours of bone (48/53), mainly H3F3A G34W variants, and in 92% of chondroblastoma (73/79), predominantly K36M mutations in H3F3B. H3F3B is paralogous to the cancer gene H3F3A. However, H3F3B driver variants have not previously been reported in human cancer. Our observation demonstrate remarkable tumour-specificity of mutations, with respect to which histone 3.3 gene and residue is mutated, indicating that the advantage these mutations confer is tumour dependent. Moreover, tumour-specific mutation of H3F3A and H3F3B suggests, that although both genes encode identical proteins, they are likely non-redundant and employed differentially during skeletal development.	Illumina HiSeq 2000	14
EGAD00001004163	Cancer genomes are frequently characterized by numerical and structural karyotypic abnormalities. Here we combined an inducible centromere-specific inactivation approach with selection for a conditionally essential gene, a strategy we term ‘CEN-SELECT’, and show that single-chromosome missegregation during cell division can directly drive a broad spectrum of structural rearrangement types. Cytogenetic profiling revealed that missegregated chromosomes are 120-fold more susceptible to developing seven major categories of structural variants, including translocations, insertions, deletions, and reassembly into chromothriptically rearranged chromosomes. Whole-genome sequencing of clones with genetically propagatable derivative chromosomes identified complex rearrangements and copy-number alterations that can result in gene inactivation or extrachromosomal gene amplification. We conclude that chromosome segregation errors are sufficient to drive extensive structural variation that recapitulates those commonly associated with human cancers.	HiSeq X Ten Illumina HiSeq 2000	22
EGAD00010000488	Chondroblastoma case sample genotype using Affymetrix SNP6.0	Affymetrix_SNP6-	7

Publications	Citations
Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Behjati S, Tarpey PS, Presneau N, Scheipl S, Pillay N, Van Loo P, Wedge DC, Cooke SL, Gundem G, Davies H, Nik-Zainal S, Martin S, McLaren S, Goodie V, Robinson B, Butler A, Teague JW, Halai D, Khatri B, Myklebost O, Baumhoer D, Jundt G, Hamoudi R, Tirabosco R, Amary MF, Futreal PA, Stratton MR, Campbell PJ, Flanagan AM. Nat Genet 45: 2013 1479-1482	599
Mutational signatures of ionizing radiation in second malignancies. Behjati S, Gundem G, Wedge DC, Roberts ND, Tarpey PS, Cooke SL, Van Loo P, Alexandrov LB, Ramakrishna M, Davies H, Nik-Zainal S, Hardy C, Latimer C, Raine KM, Stebbings L, Menzies A, Jones D, Shepherd R, Butler AP, Teague JW, Jorgensen M, Khatri B, Pillay N, Shlien A, Futreal PA, Badie C, ICGC Prostate Group, McDermott U, Bova GS, Richardson AL, Flanagan AM, Stratton MR, Campbell PJ. Nat Commun 7: 2016 12605	199
Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma. Behjati S, Tarpey PS, Haase K, Ye H, Young MD, Alexandrov LB, Farndon SJ, Collord G, Wedge DC, Martincorena I, Cooke SL, Davies H, Mifsud W, Lidgren M, Martin S, Latimer C, Maddison M, Butler AP, Teague JW, Pillay N, Shlien A, McDermott U, Futreal PA, Baumhoer D, Zaikova O, Bjerkehagen B, Myklebost O, Amary MF, Tirabosco R, Van Loo P, Stratton MR, Flanagan AM, Campbell PJ. Nat Commun 8: 2017 15936	180
Recurrent rearrangements of FOS and FOSB define osteoblastoma. Fittall MW, Mifsud W, Pillay N, Ye H, Strobl AC, Verfaillie A, Demeulemeester J, Zhang L, Berisha F, Tarabichi M, Young MD, Miranda E, Tarpey PS, Tirabosco R, Amary F, Grigoriadis AE, Stratton MR, Van Loo P, Antonescu CR, Campbell PJ, Flanagan AM, Behjati S. Nat Commun 9: 2018 2150	89
Chromosome segregation errors generate a diverse spectrum of simple and complex genomic rearrangements. Ly P, Brunner SF, Shoshani O, Kim DH, Lan W, Pyntikova T, Flanagan AM, Behjati S, Page DC, Page DC, Campbell PJ, Cleveland DW. Nat Genet 51: 2019 705-715	177
MYC amplifications are common events in childhood osteosarcoma. De Noon S, Ijaz J, Coorens TH, Amary F, Ye H, Strobl A, Lyskjaer I, Flanagan AM, Behjati S. J Pathol Clin Res 7: 2021 425-431	20
Epigenetic dysregulation from chromosomal transit in micronuclei. Agustinus AS, Al-Rawi D, Dameracharla B, Raviram R, Jones BSCL, Stransky S, Scipioni L, Luebeck J, Di Bona M, Norkunaite D, Myers RM, Duran M, Choi S, Weigelt B, Yomtoubian S, McPherson A, Toufektchan E, Keuper K, Mischel PS, Mittal V, Shah SP, Maciejowski J, Storchova Z, Gratton E, Ly P, Landau D, Bakhoum MF, Koche RP, Sidoli S, Bafna V, David Y, Bakhoum SF. Nature 619: 2023 176-183	86
Quantitative and qualitative mutational impact of ionizing radiation on normal cells. Youk J, Kwon HW, Lim J, Kim E, Kim T, Kim R, Park S, Yi K, Nam CH, Jeon S, An Y, Choi J, Na H, Lee ES, Cho Y, Min DW, Kim H, Kang YR, Choi SH, Bae MJ, Lee CG, Kim JG, Kim YS, Yu T, Lee WC, Shin JY, Lee DS, Kim TY, Ku T, Kim SY, Lee JH, Koo BK, Lee H, Yi OV, Han EC, Chang JH, Kim KS, Son TG, Ju YS. Cell Genom 4: 2024 100499	17
A breakage-replication/fusion process explains complex rearrangements and segmental DNA amplification. Zhang CZ, Mendez-Dorantes C, Burns KH, Pellman D. Nat Genet 58: 2026 88-99	0