Different patterns of clonal evolution among different sarcoma subtypes followed for up to 25 years

Jakob Hofvander (), Björn Viklund, Anders Isaksson, Otte Brosjö, Fredrik Vult von Steyern, Pehr Rissler, Nils Mandahl and Fredrik Mertens
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Jakob Hofvander: Lund University
Björn Viklund: Uppsala University
Anders Isaksson: Uppsala University
Otte Brosjö: Karolinska Hospital
Fredrik Vult von Steyern: Clinical Sciences, Lund University and Skåne University Hospital
Pehr Rissler: University and Regional Laboratories Region Skåne
Nils Mandahl: Lund University
Fredrik Mertens: Lund University

Nature Communications, 2018, vol. 9, issue 1, 1-8

Abstract: Abstract To compare clonal evolution in tumors arising through different mechanisms, we selected three types of sarcoma—amplicon-driven well-differentiated liposarcoma (WDLS), gene fusion-driven myxoid liposarcoma (MLS), and sarcomas with complex genomes (CXS)—and assessed the dynamics of chromosome and nucleotide level mutations by cytogenetics, SNP array analysis and whole-exome sequencing. Here we show that the extensive single-cell variation in WDLS has minor impact on clonal key amplicons in chromosome 12. In addition, only a few of the single nucleotide variants in WDLS were present in more than one lesion, suggesting that such mutations are of little significance in tumor development. MLS displays few mutations other than the FUS-DDIT3 fusion, and the primary tumor is genetically sometimes much more complex than its relapses, whereas CXS in general shows a gradual increase of both nucleotide- and chromosome–level mutations, similar to what has been described in carcinomas.

Date: 2018
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DOI: 10.1038/s41467-018-06098-0

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