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

Study ID Alternative Stable ID Type
EGAS00001001805 Other

Study Description

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 three years. We performed exome sequencing on germline DNA and DNA collected from tumor at three separate timepoints. We compared variant calls and variant allele frequencies between different samples. We identified subclonal driver 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 functional significance of such clones and strategies to eliminate them.

Study Datasets 1 dataset.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
Whole exome sequencing data of primary, secondary and tertiary tumor from a patient.
Illumina HiSeq 2500 4

Who archives the data?