Key clinical point: Sarcomas caused by different pathogenetic mechanisms vary considerably in the rate at which new mutations become predominant and whether nucleotide or chromosome level mutations prevail. Further, marked variation in genetic stability at the single cell level does not necessarily translate into major changes in the tumor stemline
Main finding: The extensive single-cell variation in well-differentiated liposarcoma had minor impact on clonal key amplicons in chromosome 12. Only a few of the single nucleotide variants in well-differentiated liposarcoma were present in more than one lesion, suggesting that such mutations are of little significance in tumor development. Myxoid liposarcoma displays few mutations other than the FUS-DDIT3 fusion, and the primary tumor is genetically sometimes much more complex than its relapses. Sarcomas with complex genomes have a gradual increase of both nucleotide- and chromosome–level mutations, similar to what has been described in carcinomas.
Study details: The study included 20 sarcoma patients from whom 2–5 lesions had been obtained, with 12–306 months between first and last sampling. Cytogenetics, SNP array analysis, and whole-exome sequencing were used to compare chromosome and nucleotide level mutations in 5 patients with amplicon-driven well-differentiated liposarcoma, 9 patients with gene fusion-driven myxoid liposarcoma, and 6 patients with sarcomas with complex genomes (5 myxofibrosarcomas and 1 myoepithelial tumor).
Disclosures: The authors declared no competing interests.
Source: Hofvander J et al. Nature Communications 10 Sept. 2018. https://doi.org/10.1038/s41467-018-06098-0
Hofvander J et al. Nature Communications 10 Sept. 2018. https://doi.org/10.1038/s41467-018-06098-0
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Must Reads in Liposarcoma
Type and rate of clonal evolution vary widely in sarcoma pathogenetic subgroups, Hofvander J et al. Nature Communications 10 Sept. 2018. https://doi.org/10.1038/s41467-018-06098-0
High recurrence rate after pancreaticoduodenectomy for primary retroperitoneal sarcoma, Tseng W et al. European Journal of Surgical Oncology 2018 (44): June; 810-815.
Radiotherapy benefits in surgically-treated retroperitoneal sarcoma, Nazzani S et al. Radiotherapy and Oncology 2018: 127; 318-325. https://doi.org/10.1016/j.radonc.2018.03.027
Trabectedin extended PFS in advanced liposarcoma, Le Cesne A et al. ASCO 2018. Abstract 11508.