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Expanded genetic analyses of myxofibrosarcomas may guide precision therapies

Ogura K et al. Nature Communications; 17 July 2018. https://doi.org/10.1038/s41467-018-03891-9

Key clinical point: Molecular analyses of 116 cases of myxofibrosarcomas have uncovered substantial recurrent driver genes, most of which have not been previously identified. These results can aid the development of precision medicine approaches to myxofibrosarcomas.

Main finding: The driver alterations, significantly upregulated genes, immune cell compositions, and DNA methylation pattern identified in this study will help to identify potential therapeutic targets. Novel recurrently mutated genes were found including GNAS (9%), ATRX (9%), KRAS (7%), CCND1 (6%), and JAK1 (4%), in addition to previously reported mutated genes, including TP53 (46%), RB1 (18%), CDKN2A (16%), CDKN2B (16%), NF1 (11%), NTRK1 (9%), MDM2 (6%), and PTEN (3%). Potential therapeutic targets were identified in 39% of myxofibrosarcomas. Mutations in RB1, CDKN2A/CDKN2B, and CCND1 were almost completely mutually exclusive, and defined a unique subset of myxofibrosarcomas with aberrant cell cycling and poor prognosis for which intensification or novel therapeutic approaches should be considered. The results also provide a rationale for the use of CDK4/6 inhibitors in myxofibrosarcomas harboring genetic changes in the Rb pathway, including CCND1 or CDK6 amplification.

Study details: The study cohort comprised 116 cases with MFS that underwent comprehensive and integrative molecular analyses.

Disclosures: The authors declared no competing interests.

Source: Ogura K et al. Nature Communications; 17 July 2018. https://doi.org/10.1038/s41467-018-03891-9

Citation:

Ogura K et al. Nature Communications; 17 July 2018. https://doi.org/10.1038/s41467-018-03891-9

Must Reads in Sarcoma & GIST

Intensity modulated radiation therapy may be preferable in children with extremity nonrhabdomyosarcoma soft-tissue sarcomas, Source: Rao A et al. Intl J Rad Oncology*Biology*Physics; Jan. 2019, 38-44. https://doi.org/10.1016/j.ijrobp.2018.09.005

Expanded genetic analyses of myxofibrosarcomas may guide precision therapies, Ogura K et al. Nature Communications; 17 July 2018. https://doi.org/10.1038/s41467-018-03891-9

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