Molecular and Genomic Profiling to Identify Actionable Targets in Chromophobe Renal Cell Cancer

Philip Abbosh; Srinath Sundararajan; Sherri Z Millis; Adam Hauben; Sandeep Reddy; Daniel M Geynisman; Robert Uzzo

doi:10.1016/j.euf.2017.01.003

Molecular and Genomic Profiling to Identify Actionable Targets in Chromophobe Renal Cell Cancer

Eur Urol Focus. 2018 Dec;4(6):969-971. doi: 10.1016/j.euf.2017.01.003. Epub 2017 Jan 23.

Authors

Philip Abbosh¹, Srinath Sundararajan², Sherri Z Millis³, Adam Hauben³, Sandeep Reddy³, Daniel M Geynisman⁴, Robert Uzzo¹

Affiliations

¹ Division of Urological Oncology, Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
² Division of Hematology and Oncology, Department of Medicine, University of Arizona, Tuscon, AZ, USA. Electronic address: [email protected].
³ Caris Life Sciences, Phoenix, AZ, USA.
⁴ Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.

PMID: 28753842
DOI: 10.1016/j.euf.2017.01.003

Abstract

Metastatic chromophobe renal cell cancer (chRCC) is a rare subtype of RCC with no standard treatment. We performed molecular profiling of 12 chRCC cases to identify alterations predictive of response to therapy. Tests included immunohistochemistry assays, fluorescence in situ hybridization, and next-generation sequencing. Analysis identified c-KIT overexpression in 6/9 (67%) samples analyzed, and loss of protein expression of RRM1 and MGMT in 11/12 (92%) and of PTEN in 7/12 samples (58%). Mutations of TP53, PTEN, APC, and VHL genes were identified. In summary, molecular profiling of chRCC identified alterations in genes and protein expression that might provide a mechanistic rationale for off-label use of approved therapies in advanced chRCC, and could guide the design of molecularly targeted clinical trials. PATIENT SUMMARY: In this study, we evaluated samples of a rare type of kidney cancer (chromophobe type) and identified potential genetic markers that could be used to individualize treatment and possibly improve treatment outcomes.

Keywords: Chemotherapy; Chromophobe renal carcinoma; Genetics; Molecular profiling.

Publication types

Letter

MeSH terms

Adenomatous Polyposis Coli Protein / genetics
Adult
Aged
Carcinoma, Renal Cell / genetics*
Carcinoma, Renal Cell / metabolism
Carcinoma, Renal Cell / pathology
DNA Modification Methylases / metabolism
DNA Repair Enzymes / metabolism
DNA Topoisomerases, Type II / genetics
ErbB Receptors / genetics
Female
Genomics
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Kidney Neoplasms / genetics*
Kidney Neoplasms / metabolism
Kidney Neoplasms / pathology
Male
Middle Aged
Molecular Targeted Therapy
Mutation
Neoplasm Metastasis
Neoplasm Staging
PTEN Phosphohydrolase / genetics
PTEN Phosphohydrolase / metabolism
Poly-ADP-Ribose Binding Proteins / genetics
Proto-Oncogene Proteins c-kit / metabolism
Receptor, ErbB-2 / genetics
Ribonucleoside Diphosphate Reductase
Sequence Analysis, DNA
Transcriptome
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Proteins / metabolism
Von Hippel-Lindau Tumor Suppressor Protein / genetics

Substances

APC protein, human
Adenomatous Polyposis Coli Protein
Poly-ADP-Ribose Binding Proteins
TP53 protein, human
Tumor Suppressor Protein p53
Tumor Suppressor Proteins
RRM1 protein, human
Ribonucleoside Diphosphate Reductase
DNA Modification Methylases
MGMT protein, human
Von Hippel-Lindau Tumor Suppressor Protein
EGFR protein, human
ERBB2 protein, human
ErbB Receptors
KIT protein, human
Proto-Oncogene Proteins c-kit
Receptor, ErbB-2
PTEN Phosphohydrolase
PTEN protein, human
DNA Topoisomerases, Type II
TOP2A protein, human
VHL protein, human
DNA Repair Enzymes