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

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

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	English
Pages (from-to)	969-971
Number of pages	3
Journal	European Urology Focus
Volume	4
Issue number	6
DOIs	https://doi.org/10.1016/j.euf.2017.01.003
State	Published - Dec 2018

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.euf.2017.01.003

Cite this

@article{554d2bbe49304bbbbc7c94ed52d1162b,

title = "Molecular and Genomic Profiling to Identify Actionable Targets in Chromophobe Renal Cell Cancer",

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

author = "Philip Abbosh and Srinath Sundararajan and Millis, {Sherri Z.} and Adam Hauben and Sandeep Reddy and Geynisman, {Daniel M.} and Robert Uzzo",

year = "2018",

month = dec,

doi = "10.1016/j.euf.2017.01.003",

language = "English",

volume = "4",

pages = "969--971",

journal = "European Urology Focus",

issn = "2405-4569",

publisher = "Elsevier B.V.",

number = "6",

}

TY - JOUR

T1 - Molecular and Genomic Profiling to Identify Actionable Targets in Chromophobe Renal Cell Cancer

AU - Abbosh, Philip

AU - Sundararajan, Srinath

AU - Millis, Sherri Z.

AU - Hauben, Adam

AU - Reddy, Sandeep

AU - Geynisman, Daniel M.

AU - Uzzo, Robert

PY - 2018/12

Y1 - 2018/12

N2 - 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.

AB - 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.

KW - Chemotherapy

KW - Chromophobe renal carcinoma

KW - Genetics

KW - Molecular profiling

KW - Immunohistochemistry

KW - Ribonucleoside Diphosphate Reductase

KW - DNA Topoisomerases, Type II/genetics

KW - DNA Modification Methylases/metabolism

KW - Genomics

KW - Humans

KW - Middle Aged

KW - Transcriptome

KW - Male

KW - Molecular Targeted Therapy

KW - Poly-ADP-Ribose Binding Proteins/genetics

KW - Neoplasm Metastasis

KW - Kidney Neoplasms/genetics

KW - Adenomatous Polyposis Coli Protein/genetics

KW - Adult

KW - Female

KW - Tumor Suppressor Proteins/metabolism

KW - In Situ Hybridization, Fluorescence

KW - Receptor, ErbB-2/genetics

KW - Tumor Suppressor Protein p53/genetics

KW - Proto-Oncogene Proteins c-kit/metabolism

KW - Sequence Analysis, DNA

KW - Carcinoma, Renal Cell/genetics

KW - DNA Repair Enzymes/metabolism

KW - ErbB Receptors/genetics

KW - PTEN Phosphohydrolase/genetics

KW - Von Hippel-Lindau Tumor Suppressor Protein/genetics

KW - Aged

KW - High-Throughput Nucleotide Sequencing

KW - Mutation

KW - Neoplasm Staging

UR - http://www.scopus.com/inward/record.url?scp=85010006356&partnerID=8YFLogxK

U2 - 10.1016/j.euf.2017.01.003

DO - 10.1016/j.euf.2017.01.003

M3 - Article

C2 - 28753842

SN - 2405-4569

VL - 4

SP - 969

EP - 971

JO - European Urology Focus

JF - European Urology Focus

IS - 6

ER -

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

Abstract

Keywords

UN SDGs

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