Unforeseen clonal evolution of tumor cell population in recurrent and metastatic dermatofibrosarcoma protuberans

Ensel Oh, Hae Min Jeong, Mi Jeong Kwon, Sang Yun Ha, Hyung Kyu Park, Ji Young Song, Yu Jin Kim, Jong Sun Choi, Eun Hee Lee, Jeeyun Lee, Yoon La Choi, Young Kee Shin

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Article numbere0185826
JournalPLoS ONE
Volume12
Issue number10
DOIs
StatePublished - Oct 2017

Fingerprint

Dive into the research topics of 'Unforeseen clonal evolution of tumor cell population in recurrent and metastatic dermatofibrosarcoma protuberans'. Together they form a unique fingerprint.

Cite this