Genetic basis of progression and relapse in Clear Cell Sarcoma of the Kidney

To elucidate the genetic mechanisms of recurrence and metastasis in clear cell sarcoma of the kidney (CCSK), a dismal pediatric renal cancer, we performed targeted-capture sequencing by pediatric solid tumors panel (381 genes) for multi-sampled tumors including autopsy samples of metastasis extracted from a single case that underwent four relapses. Internal tandem duplication of BCOR (BCOR-ITD) was the only truncal mutation, indicating a strong association with tumorigenesis. Acquisition of additional mutations along tumor relapses and detection of metastasis-specific mutations were reminiscent of the tumor progression and therapeutic resistance of this case, leading to clonal selection and a dismal fate.