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

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 seria...

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Bibliographic Details
Published in:PloS one 2017-10, Vol.12 (10), p.e0185826-e0185826
Main Authors: Oh, Ensel, Jeong, Hae Min, Kwon, Mi Jeong, Ha, Sang Yun, Park, Hyung Kyu, Song, Ji-Young, Kim, Yu Jin, Choi, Jong-Sun, Lee, Eun Hee, Lee, Jeeyun, Choi, Yoon-La, Shin, Young Kee
Format: Article
Language:English
Subjects:
Apoptosis
Bioinformatics
Biology and Life Sciences
Chromosome rearrangements
Chromosomes
Clonal Evolution
Cloning
Collagen (type I)
Collagen Type I - genetics
Copy number
Dermatofibrosarcoma - genetics
Dermatofibrosarcoma - pathology
Dermatofibrosarcoma protuberans
Evolution
Fusion protein
Gene Fusion
Genomes
Genomics
Growth factors
Health sciences
Humans
Imatinib
Kinases
Laboratories
Lung cancer
Male
Malignancy
Medicine
Medicine and Health Sciences
Metastases
Metastasis
Middle Aged
Mutation
Neoplasm Metastasis
Pathology
Patients
Pharmacy
Proto-Oncogene Proteins c-sis - genetics
Recurrence
Research and Analysis Methods
Sarcoma
Soft tissue sarcoma
Studies
Target recognition
Tumors
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0185826