Abstract
Dermatofibrosarcoma protuberans (DFSP) is a very rare soft tissue sarcoma, generally of low-grade malignancy. DFSP is locally aggressive with a high recurrence rate, but metastasis occurs rarely. To investigate the mechanism of metastasis in DFSP, we analyzed the whole exome sequencing data of serial tumor samples obtained from a patient who had a 10-year history of recurrent and metastatic DFSP. Tracking various genomic alterations, namely somatic mutations, copy number variations, and chromosomal rearrangements, we observed a dramatic change in tumor cell population during the occurrence of metastasis in this DFSP case. The new subclone that emerged in metastatic DFSP harbored a completely different set of somatic mutations and new focal amplifications, which had not been observed in the primary clone before metastasis. The COL1A1-PDGFB fusion, characteristic of DFSP, was found in all of the serial samples. Moreover, the break position on the fusion gene was identical in all samples. Based on these observations, we suggest a clonal evolution model to explain the mechanism underlying metastasis in DFSP and identified several candidate target genes responsible for metastatic DFSP by utilizing The Cancer Genome Atlas database. This is the first study to observe clonal evolution in metastatic DFSP and provide insight for a possible therapeutic strategy for imatinib-resistant or metastatic DFSP.
Highlights
It is increasingly accepted that tumor progression is driven by sequential selection of more aggressive subclones known as “cancer-clone evolution” [1]
The resistant clones in colon cancer patients, who initially benefited from EGFR blockade but experienced disease progression thereafter, often harbored mutations in KRAS, which were absent before the start of the therapy
The patient was diagnosed with Dermatofibrosarcoma protuberans (DFSP) in 2007 on the basis of the presence of collagen 1 alpha 1 (COL1A1)-PDGFRB fusion revealed by fluorescence in situ hybridization (FISH)
Summary
It is increasingly accepted that tumor progression is driven by sequential selection of more aggressive subclones known as “cancer-clone evolution” [1] This is a process similar to Darwinian natural selection wherein individuals with certain variants of a trait survive and reproduce at a higher rate than others with less advantageous variants do. More sensitive detection methods increasingly suggest that these mutations exist in a small number of cells within the primary tumor population before treatment and become the dominant clones owing to the drug selection pressure [4, 6] These observations indicate that tumor evolution can affect therapeutic decisions and patient outcomes. It is crucial to identify genetically distinct subclones at diagnosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
