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Identifying_new_diagnostic_and_treatment_pathways_for_patients_with_unclassifiable_sarcomas

Whole genome sequencing of tumour normal pairs of human undifferentiated sarcomas.

Type: Cancer Genomics
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 3 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001003216	Whole genome sequencing of tumour normal pairs of human undifferentiated sarcomas.	HiSeq X Ten	98
EGAD00001004162	Undifferentiated sarcomas (USARC) of adults are diverse, rare and aggressive soft tissue cancers. Recent efforts have confirmed that USARC exhibit one of the highest burdens of structural aberrations across human cancer. Here, we sought to unravel the genomic basis of this structural complexity by integrating whole genome sequencing, ploidy analysis and methylation profiling of 53 USARC. We identified whole genome doubling as a prevalent and pernicious force in USARC tumourigenesis. Deconvolution of the complex copy number and rearrangement landscapes show distinct signatures associated with chromothripsis, early-haploidy, and successive whole-genome-doubling events, suggesting four divergent models of sarcoma development. We show similar distinct evolutionary tumourigenic pathways in different sarcoma subtypes from the Cancer Genome Atlas. Thirteen percent of tumours exhibited a hypermutator phenotype, opening new avenues for clinical management such as immunotherapy, whilst the period prior to and between genome doubling events may represent clinically relevant interventional points in USARC.	HiSeq X Ten	56

Publications	Citations
Undifferentiated Sarcomas Develop through Distinct Evolutionary Pathways. Steele CD, Tarabichi M, Oukrif D, Webster AP, Ye H, Fittall M, Lombard P, Martincorena I, Tarpey PS, Collord G, Haase K, Strauss SJ, Berisha F, Vaikkinen H, Dhami P, Jansen M, Behjati S, Amary MF, Tirabosco R, Feber A, Campbell PJ, Alexandrov LB, Van Loo P, Flanagan AM, Pillay N. Cancer Cell 35: 2019 441-456.e8	56
Mapping clustered mutations in cancer reveals APOBEC3 mutagenesis of ecDNA. Bergstrom EN, Luebeck J, Petljak M, Khandekar A, Barnes M, Zhang T, Steele CD, Pillay N, Landi MT, Bafna V, Mischel PS, Harris RS, Alexandrov LB. Nature 602: 2022 510-517	51
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	0