Molecular dissection of complete response to receptor tyrosine kinase inhibition in type II papillary renal cell carcinoma

Matti Annala, Lucia Nappi, Arun A Azad, Fan Mo, Ladan Fazli, Kim N Chi, Alexander W Wyatt

Research output: Contribution to journalArticleOtherpeer-review


Metastatic papillary renal cell carcinoma (pRCC) is invariably lethal. Receptor tyrosine kinase inhibitors such as sunitinib malate are demonstrated to prolong survival but resistance is inevitable and clinical responses greater than one year are very rare. Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare inherited disorder caused by germline mutation to the fumarate hydratase (FH) gene and characterized in part by FH-deficient pRCC tumors that are particularly aggressive. We present a remarkable case of FH-deficient metastatic pRCC who has experienced an 8 year complete response to receptor tyrosine kinase inhibitors sunitinib malate and pazopanib. We performed exome sequencing on her primary and metastatic tumors and reveal relevant genomic alterations including amplification of the growth factor effector GRB2, and mutations to critical DNA damage repair genes that are not normally perturbed in pRCC or indeed renal cell carcinoma (RCC) in general. We posit that defects to these genes and pathways could influence the response of RCC to RTK inhibitors, and that other RCC patients with strong response to therapy should be evaluated for similar genomic aberrations.
Original languageEnglish
Pages (from-to)e145-e150
Number of pages6
JournalClinical Genitourinary Cancer
Issue number1
Publication statusPublished - Feb 2017


  • DNA damage repair
  • fumarate hydratase
  • hereditary leiomyomatosis and renal cell cancer
  • Pazopanib
  • Sunitinib

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