Genomic Profile of Urothelial Carcinoma of the Upper Tract from Ureteroscopic Biopsy: Feasibility and Validation Using Matched Radical Nephroureterectomy Specimens

Aditya Bagrodia, Francois Audenet, Eugene J. Pietzak, Kwanghee Kim, Katie S. Murray, Eugene K. Cha, John P. Sfakianos, Gopa Iyer, Nirmish Singla, Maria Arcila, Bernard H. Bochner, Hikmat A. Al-Ahmadie, David B. Solit, Jonathan A. Coleman

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Urothelial carcinoma of the upper tract (UTUC) presents specific challenges regarding accurate staging and tumor sampling. We aimed to assess the feasibility of applying next-generation sequencing to biopsy specimens and gauged the concordance of their genetic profiles with matched radical nephroureterectomy (RNU) specimens. Of the 39 biopsy specimens collected, 36 (92%) had adequate material for sequencing using a hybridization-based exon capture assay (MSK-IMPACT). The most frequently altered genes across the patient cohort were consistent with the urothelial carcinoma-associated alterations identified in a cohort of 130 RNU specimens previously sequenced at our center, including mutations in the TERT promoter (64%), hotspot activating mutations in FGFR3 (64%), and frequent mutations in chromatin remodeling genes. For 12 patients, a matching tumor sample from a subsequent RNU was sequenced. We found a high level of concordance between matched biopsy and RNU specimens, up to 92% for the likely pathogenic alterations. Patient summary: We evaluated the feasibility of genomic characterization of tumor tissue collected at the time of ureteroscopic biopsy and found high concordance with subsequent radical nephroureterectomy specimens. Molecular characterization of urothelial carcinoma of the upper tract biopsies could guide treatment decision-making and identify high-risk patients who could benefit from neoadjuvant chemotherapy and low-risk patients who could benefit from conservative or organ-sparing strategies. Urothelial carcinoma of the upper tract presents specific challenges for diagnosis and treatment strategies. We demonstrated that next-generation sequencing is feasible for ureteroscopic biopsy specimens and concordant with radical nephroureterectomy specimens. This could guide treatment decisions.

Original languageEnglish (US)
JournalEuropean Urology Focus
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Carcinoma
Biopsy
Mutation
Chromatin Assembly and Disassembly
Neoplasm Staging
Genes
Exons
Neoplasms
Decision Making
Therapeutics
Drug Therapy

Keywords

  • Biomarkers
  • Genomics
  • Prediction
  • Transitional cell carcinoma
  • Upper tract urothelial carcinoma

ASJC Scopus subject areas

  • Urology

Cite this

Genomic Profile of Urothelial Carcinoma of the Upper Tract from Ureteroscopic Biopsy : Feasibility and Validation Using Matched Radical Nephroureterectomy Specimens. / Bagrodia, Aditya; Audenet, Francois; Pietzak, Eugene J.; Kim, Kwanghee; Murray, Katie S.; Cha, Eugene K.; Sfakianos, John P.; Iyer, Gopa; Singla, Nirmish; Arcila, Maria; Bochner, Bernard H.; Al-Ahmadie, Hikmat A.; Solit, David B.; Coleman, Jonathan A.

In: European Urology Focus, 01.01.2018.

Research output: Contribution to journalArticle

Bagrodia, A, Audenet, F, Pietzak, EJ, Kim, K, Murray, KS, Cha, EK, Sfakianos, JP, Iyer, G, Singla, N, Arcila, M, Bochner, BH, Al-Ahmadie, HA, Solit, DB & Coleman, JA 2018, 'Genomic Profile of Urothelial Carcinoma of the Upper Tract from Ureteroscopic Biopsy: Feasibility and Validation Using Matched Radical Nephroureterectomy Specimens', European Urology Focus. https://doi.org/10.1016/j.euf.2018.01.005
Bagrodia, Aditya ; Audenet, Francois ; Pietzak, Eugene J. ; Kim, Kwanghee ; Murray, Katie S. ; Cha, Eugene K. ; Sfakianos, John P. ; Iyer, Gopa ; Singla, Nirmish ; Arcila, Maria ; Bochner, Bernard H. ; Al-Ahmadie, Hikmat A. ; Solit, David B. ; Coleman, Jonathan A. / Genomic Profile of Urothelial Carcinoma of the Upper Tract from Ureteroscopic Biopsy : Feasibility and Validation Using Matched Radical Nephroureterectomy Specimens. In: European Urology Focus. 2018.
@article{a35a2c51a03346a882497a7a85ebf565,
title = "Genomic Profile of Urothelial Carcinoma of the Upper Tract from Ureteroscopic Biopsy: Feasibility and Validation Using Matched Radical Nephroureterectomy Specimens",
abstract = "Urothelial carcinoma of the upper tract (UTUC) presents specific challenges regarding accurate staging and tumor sampling. We aimed to assess the feasibility of applying next-generation sequencing to biopsy specimens and gauged the concordance of their genetic profiles with matched radical nephroureterectomy (RNU) specimens. Of the 39 biopsy specimens collected, 36 (92{\%}) had adequate material for sequencing using a hybridization-based exon capture assay (MSK-IMPACT). The most frequently altered genes across the patient cohort were consistent with the urothelial carcinoma-associated alterations identified in a cohort of 130 RNU specimens previously sequenced at our center, including mutations in the TERT promoter (64{\%}), hotspot activating mutations in FGFR3 (64{\%}), and frequent mutations in chromatin remodeling genes. For 12 patients, a matching tumor sample from a subsequent RNU was sequenced. We found a high level of concordance between matched biopsy and RNU specimens, up to 92{\%} for the likely pathogenic alterations. Patient summary: We evaluated the feasibility of genomic characterization of tumor tissue collected at the time of ureteroscopic biopsy and found high concordance with subsequent radical nephroureterectomy specimens. Molecular characterization of urothelial carcinoma of the upper tract biopsies could guide treatment decision-making and identify high-risk patients who could benefit from neoadjuvant chemotherapy and low-risk patients who could benefit from conservative or organ-sparing strategies. Urothelial carcinoma of the upper tract presents specific challenges for diagnosis and treatment strategies. We demonstrated that next-generation sequencing is feasible for ureteroscopic biopsy specimens and concordant with radical nephroureterectomy specimens. This could guide treatment decisions.",
keywords = "Biomarkers, Genomics, Prediction, Transitional cell carcinoma, Upper tract urothelial carcinoma",
author = "Aditya Bagrodia and Francois Audenet and Pietzak, {Eugene J.} and Kwanghee Kim and Murray, {Katie S.} and Cha, {Eugene K.} and Sfakianos, {John P.} and Gopa Iyer and Nirmish Singla and Maria Arcila and Bochner, {Bernard H.} and Al-Ahmadie, {Hikmat A.} and Solit, {David B.} and Coleman, {Jonathan A.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.euf.2018.01.005",
language = "English (US)",
journal = "European Urology Focus",
issn = "2405-4569",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Genomic Profile of Urothelial Carcinoma of the Upper Tract from Ureteroscopic Biopsy

T2 - Feasibility and Validation Using Matched Radical Nephroureterectomy Specimens

AU - Bagrodia, Aditya

AU - Audenet, Francois

AU - Pietzak, Eugene J.

AU - Kim, Kwanghee

AU - Murray, Katie S.

AU - Cha, Eugene K.

AU - Sfakianos, John P.

AU - Iyer, Gopa

AU - Singla, Nirmish

AU - Arcila, Maria

AU - Bochner, Bernard H.

AU - Al-Ahmadie, Hikmat A.

AU - Solit, David B.

AU - Coleman, Jonathan A.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Urothelial carcinoma of the upper tract (UTUC) presents specific challenges regarding accurate staging and tumor sampling. We aimed to assess the feasibility of applying next-generation sequencing to biopsy specimens and gauged the concordance of their genetic profiles with matched radical nephroureterectomy (RNU) specimens. Of the 39 biopsy specimens collected, 36 (92%) had adequate material for sequencing using a hybridization-based exon capture assay (MSK-IMPACT). The most frequently altered genes across the patient cohort were consistent with the urothelial carcinoma-associated alterations identified in a cohort of 130 RNU specimens previously sequenced at our center, including mutations in the TERT promoter (64%), hotspot activating mutations in FGFR3 (64%), and frequent mutations in chromatin remodeling genes. For 12 patients, a matching tumor sample from a subsequent RNU was sequenced. We found a high level of concordance between matched biopsy and RNU specimens, up to 92% for the likely pathogenic alterations. Patient summary: We evaluated the feasibility of genomic characterization of tumor tissue collected at the time of ureteroscopic biopsy and found high concordance with subsequent radical nephroureterectomy specimens. Molecular characterization of urothelial carcinoma of the upper tract biopsies could guide treatment decision-making and identify high-risk patients who could benefit from neoadjuvant chemotherapy and low-risk patients who could benefit from conservative or organ-sparing strategies. Urothelial carcinoma of the upper tract presents specific challenges for diagnosis and treatment strategies. We demonstrated that next-generation sequencing is feasible for ureteroscopic biopsy specimens and concordant with radical nephroureterectomy specimens. This could guide treatment decisions.

AB - Urothelial carcinoma of the upper tract (UTUC) presents specific challenges regarding accurate staging and tumor sampling. We aimed to assess the feasibility of applying next-generation sequencing to biopsy specimens and gauged the concordance of their genetic profiles with matched radical nephroureterectomy (RNU) specimens. Of the 39 biopsy specimens collected, 36 (92%) had adequate material for sequencing using a hybridization-based exon capture assay (MSK-IMPACT). The most frequently altered genes across the patient cohort were consistent with the urothelial carcinoma-associated alterations identified in a cohort of 130 RNU specimens previously sequenced at our center, including mutations in the TERT promoter (64%), hotspot activating mutations in FGFR3 (64%), and frequent mutations in chromatin remodeling genes. For 12 patients, a matching tumor sample from a subsequent RNU was sequenced. We found a high level of concordance between matched biopsy and RNU specimens, up to 92% for the likely pathogenic alterations. Patient summary: We evaluated the feasibility of genomic characterization of tumor tissue collected at the time of ureteroscopic biopsy and found high concordance with subsequent radical nephroureterectomy specimens. Molecular characterization of urothelial carcinoma of the upper tract biopsies could guide treatment decision-making and identify high-risk patients who could benefit from neoadjuvant chemotherapy and low-risk patients who could benefit from conservative or organ-sparing strategies. Urothelial carcinoma of the upper tract presents specific challenges for diagnosis and treatment strategies. We demonstrated that next-generation sequencing is feasible for ureteroscopic biopsy specimens and concordant with radical nephroureterectomy specimens. This could guide treatment decisions.

KW - Biomarkers

KW - Genomics

KW - Prediction

KW - Transitional cell carcinoma

KW - Upper tract urothelial carcinoma

UR - http://www.scopus.com/inward/record.url?scp=85041218779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041218779&partnerID=8YFLogxK

U2 - 10.1016/j.euf.2018.01.005

DO - 10.1016/j.euf.2018.01.005

M3 - Article

C2 - 29396293

AN - SCOPUS:85041218779

JO - European Urology Focus

JF - European Urology Focus

SN - 2405-4569

ER -