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of patients in our series had CGP performed on primary
tumor tissue. Temporally, the genomic profile for a patient
at the time of primary tumor collection may be distinct
from the profile at the onset of metastatic disease,
although the oncogenic drivers are preserved from
primary to metastasis, as seen in multiple studies in
different tumors . A recent report assessing
circulating tumor DNA from 224 patients with advanced
RCC noted an increase in selected alterations (TP53, VHL,
NF1, EGFR, and PIK3CA) from first- to second-line therapy
Notably, however, only a small minority of the study
patients had PRCC.
5. Conclusions
The data set reported here represents the largest to date in
characterizing patients with PRCC using CGP. In contrast to
the TCGA experience, our cohort primarily comprised
patients with advanced disease, with > 80% characterized
as stage III or IV. The most prevalent alterations in our series
(including MET, CKDN2A/B, and SWI/SNF pathway altera-
tions) could be linked to targeted therapies currently being
explored in the clinic, and other selected alterations (such as
NF1) may identify patients who are predisposed to benefit
from existing VEGF- and mTOR-directed therapies. Recent
studies exploring VEGF- and mTOR-directed therapies in
unselected patients with metastatic PRCC have produced
modest results . Use of CGP and the development of a
personalized approach for advanced PRCC may be a highly
promising approach.
Author contributions: Sumanta K. Pal had full access to all the data in the
study and takes responsibility for the integrity of the data and the accuracy
of the data analysis.
Study concept and design: Pal, Ali, Karam, Choueiri, Chung, Stephens, Ross,
Miller.
Acquisition of data: Pal, Yakirevich, Geynisman, Huang, Agarwal, Shuch,
Choueiri, Chung.
Analysis and interpretation of data: Pal, Ali, Elvin, Frampton, Lin,
Rosenzweig, Lipson, Stephens.
Drafting of the manuscript: Pal, Ali, Karam, Choueiri, Chung.
Critical revision of the manuscript for important intellectual content: Pal, Ali,
Karam, Choueiri, Chung.
Statistical analysis: Pal, Ali, Karam, Choueiri, Chung.
Obtaining funding: None.
Administrative, technical, or material support: None.
Supervision: Pal, Ali, Karam, Stephens, Ross, Miller, Agarwal, Choueiri,
Chung.
Other: None.
Financial disclosures: Sumanta K. Pal certifies that all conflicts of
interest, including specific financial interests and relationships and
affiliations relevant to the subject matter or materials discussed in the
manuscript (eg, employment/affiliation, grants or funding, consultan-
cies, honoraria, stock ownership or options, expert testimony, royalties,
or patents filed, received, or pending), are the following: Siraj M. Ali, Julia
A. Elvin, Garrett M. Frampton, Mark Rosenzweig, Doron Lipson, Philip J.
Stephens, Jeffrey S. Ross, Vincent A. Miller, and Jon H. Chung are
employees of and hold equity interest in Foundation Medicine.
Funding/Support and role of the sponsor: None.
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at
.
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