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

ABSTRACT: 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 subclo

SUBMITTER: Chen KS 

PROVIDER: S-EPMC5002927 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature