Background: Papillary renal cell carcinoma type 2 (PRCC2) is refractory to systemic treatment and has a dismal prognosis. Previous studies showed that genetic alterations in PRCC2 were heterogeneous regardless of germline or somatic mutations. In this study, we aimed to perform precision treatment of PRCC2 based on genetic information.
Methods: We performed exome and genome sequencing of tumor tissues and matched normal samples. Based on sequencing data, we treated patients with metastatic PRCC2 using precision oncology.
Results: Four patients underwent curative surgery of PRCC2 and three patients had metastatic PRCC2. All PRCC2 heterogeneously harbored own driver mutations. Two out of the three patients with metastatic disease had fumarate hydratase (FH) germline mutations. One patient with a germline FH mutation was diagnosed with hereditary leiomyomatosis RCC. He was treated with bevacizumab and erlotinib combination and showed a durable response. The other metastatic PRCC2 patient harboring a germline FH mutation had an additional somatic FH mutation and was durably controlled with pazopanib. Other metastatic PRCC2 patient with somatic PBRM1 and SETD2 mutations had over 5 years of overall survival with axitinib treatment.
Conclusions: We performed precision systemic treatment based on genetic information. Genome sequencing could help identify candidates for targeted therapy in PRCC2, a genetically heterogeneous disease.
Keywords: Whole genome sequencing; fumarate hydratase (FH); papillary renal cell carcinoma type 2 (PRCC2); precision oncology; vascular endothelial growth factor-receptor (VEGFR).
2020 Annals of Translational Medicine. All rights reserved.