EURURO Vol. 73 No. 1

71 148

Platinum Priority – Kidney Cancer
Editorial by Ronan Flippot, Eva Compe´rat, Nizar M. Tannir and Gabriel G. Malouf on pp. 79–80 of this issue
Characterization of Clinical Cases of Advanced Papillary
Renal Cell Carcinoma via Comprehensive Genomic Profiling
Sumanta K. Pal Siraj M. Ali y, Evgeny Yakirevich Daniel M. Geynisman
Jose A. Karam Julia A. Elvin Garrett M. Frampton Xuan Huang Douglas I. Lin
Mark Rosenzweig Doron Lipson Philip J. Stephens Jeffrey S. Ross Vincent A. Miller
Neeraj Agarwal Brian Shuch Toni K. Choueiri , Jon H. Chung
a Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; bFoundation Medicine,
Cambridge, MA, USA; c Department of Pathology, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, USA; dDepartment of
Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA; e Department of Urology, University of Texas MD Anderson Cancer Center, Houston,
TX, USA; f Division of Hematology and Oncology, University Hospitals Case Medical Center & Case Western Reserve University, Cleveland, OH, USA;
g Department of Pathology, Beth Israel Deaconess Medical Center, Chelsea, MA, USA; h Department of Pathology and Laboratory Medicine, Albany Medical
College, Albany, NY, USA; i Division of Medical Oncology, Department of Internal Medicine, University of Utah Huntsman Cancer Institute, Salt Lake City, UT,
USA; j Division of Urology, Yale Cancer Institute, New Haven, CT, USA; k Division of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA
ava ilable at
journal homepage:
Article info
Article history:
Accepted May 17, 2017
Associate Editor:
James Catto
Keywords:
Genomic profiling
Mutational burden
Papillary renal cell carcinoma
Abstract
Background: Papillary renal cell carcinoma (PRCC) is a rare subset of RCC. The Cancer
Genome Atlas (TCGA) data largely reflect localized disease, and there are limited data for
advanced PRCC.
Objective: To characterize the frequency of genomic alterations (GAs) in patients with
advanced PRCC for whom comprehensive genomic profiling (CGP) was performed in the
context of routine clinical care.
Design, setting, and participants: Formalin-fixed, paraffin-embedded tissue was
obtained for 169 consecutive patients with confirmed PRCC. DNA was extracted and
comprehensive genomic profiling was performed in a certified central laboratory.
Measurements: Hybrid-capture, adaptor ligation-based libraries of up to 315 genes were
sequenced to a median coverage of 648 . All classes of GAs were identified, including
substitutions, insertions/deletions, copy number alterations, and rearrangements.
Results and limitations: From 169 patients, either primary tumor tissue (102 patients,
60%) or metastatic tissue (67 patients, 40%) was collected. In patients with type 1 PRCC,
commonly altered genes were MET (33%; 8 activating mutations, 5 amplifications at
> 6 copies), TERT (30%), CDKN2A/B (13%), and EGFR (8%). In patients with type 2 PRCC,
commonly altered genes were CDKN2A/B (18%), TERT (18%), NF2 (13%), and FH (13%);
MET GAs (5 mutations, 3 amplifications) were observed in 7% of type 2 cases. Notable
differences from TCGA data include higher frequencies of MET, NF2 , and CDKN2A/B GAs,
y These authors contributed equally to this work.
* Corresponding author. Department of Medical Oncology & Experimental Therapeutics, City of Hope
Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USA. Tel.+1 626 2564673;
Fax: +1 626 3018233.
E-mail address: (S.K. Pal).
** Corresponding author. Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02115,
USA. Tel. +1 617 6325456; Fax: +1 617 6322165.
E-mail address: (T.C. Choueiri).
0302-2838/# 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.