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A novel TP53-KPNA3 translocation defines a de novo treatment-resistant clone in osteosarcoma

 Kenneth S. Chen  ;  Woo Sun Kwon  ;  Jiwoong Kim  ;  Su Jin Heo  ;  Hyo Song Kim  ;  Hyo Ki Kim  ;  Soo Hee Kim  ;  Won Suk Lee  ;  Hyun Cheol Chung  ;  Sun Young Rha  ;  Tae Hyun Hwang 
 Cold Spring Harbor Perspectives in Medicine, Vol.2(5) : a000992, 2016 
Journal Title
 Cold Spring Harbor Perspectives in Medicine 
Issue Date
Osteosarcoma is the most common primary bone cancer. It can be cured by aggressive surgery and chemotherapy, but outcomes for metastatic or chemoresistant disease remain dismal. Cancer sequencing studies have shown that the p53 pathway is dysregulated in nearly every case, often by translocation; however, no studies of osteosarcoma evolution or intratumor heterogeneity have been done to date. We studied a patient with chemoresistant, metastatic disease over the course of 3 years. We performed exome sequencing on germline DNA and DNA collected from tumor at three separate time points. We compared variant calls and variant allele frequencies between different samples. We identified subclonal mutations in several different genes in the primary tumor sample and found that one particular subclone dominated subsequent tumor samples at relapse. This clone was marked by a novel TP53-KPNA3 translocation and loss of the opposite-strand wild-type TP53 allele. Future research must focus on the functional significance of such clones and strategies to eliminate them.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
권우선(Kwon, Woo Sun)
김효송(Kim, Hyo Song) ORCID logo https://orcid.org/0000-0002-0625-9828
라선영(Rha, Sun Young) ORCID logo https://orcid.org/0000-0002-2512-4531
정현철(Chung, Hyun Cheol) ORCID logo https://orcid.org/0000-0002-0920-9471
허수진(Heo, Su Jin) ORCID logo https://orcid.org/0000-0002-0615-5869
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