A Global and Integrated Analysis of CINSARC-Associated Genetic Defects

The Complexity Index in Sarcomas (CINSARC) signature is a transcriptomic marker that identifies high-risk soft-tissue sarcomas and is associated with high metastatic potential. During the last decade, CINSARC has been successfully developed and validated and is currently being assessed in two prospe...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2020-12, Vol.80 (23), p.5282-5290
Main Authors: Lesluyes, Tom, Chibon, Frédéric
Format: Article
Language:English
Subjects:
Aged
Biomarkers, Tumor - genetics
DNA Copy Number Variations
DNA Methylation
Female
Gene Expression Regulation, Neoplastic
Humans
Male
MicroRNAs - genetics
Middle Aged
Prognosis
Sarcoma - genetics
Sarcoma - pathology
Whole Genome Sequencing
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Summary:The Complexity Index in Sarcomas (CINSARC) signature is a transcriptomic marker that identifies high-risk soft-tissue sarcomas and is associated with high metastatic potential. During the last decade, CINSARC has been successfully developed and validated and is currently being assessed in two prospective phase III clinical trials for stratification of therapy. Although the link between CINSARC expression and tumor aggressiveness is well established, questions remain about how CINSARC genes are regulated. In this study, we leveraged a The Cancer Genome Atlas multiomics study on sarcomas with complex genetics to appraise the association between CINSARC profile, genomic features, and two potential regulation mechanisms, DNA methylation and miRNA expression. CINSARC expression was associated with an increase of ploidy, intratumor heterogeneity, copy-number alteration, altered expression of 37 miRNAs, and a decrease of DNA methylation. These genetic changes are not independent, but rather act together to promote or repress CINSARC expression. These findings depict new insights into CINSARC regulation. SIGNIFICANCE: These findings demonstrate that CINSARC is associated with a variety of genomic aberrations that contribute to higher risk for metastasis and may serve as a prognostic factor in sarcomas and beyond.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-20-0512