Grade progression in urothelial carcinoma can occur with high or low mutational homology

A first-step toward tumor-specific care in initial low-grade bladder cancer

Ralf Kittler, Christine Shiang, Ryan Craig Hutchinson, Rahul K. Kollipara, Payal Kapur, Franto Francis, Yair Lotan

Research output: Contribution to journalArticle

Abstract

Purpose: Low-grade (LG) urothelial carcinomas of the bladder (UCB) are common malignancies that are costly to surveil and rarely progress to life threatening, highgrade (HG) malignancies. It is unknown if the progression of LG to HG is a result of second primary tumors or transformation of existing LG tumors. We examined tumor genetics in patients with grade progression in urothelial carcinoma and compared to patients with no progression. Results: Five patients were identified with progression. Median time from initial LG diagnosis to HG diagnosis in those experiencing progression was 19 months. Progression with both high and low mutational homology was identified. Gene alterations associated with tumor grade progression in initial low grade tumors include FBN3, CIT and HECTD4. Materials and Methods: An institutional cancer database at a tertiary referral center in the United States identified patients who progressed from LG to HG UCB. Histologic re-review was performed by a genitourinary pathologist. Whole exome sequencing with correction for germline mutations by buffy coat subtraction was performed. Mutations were assessed between LG tumors and subsequent samepatient HG tumors and for LG patients who did not progress. Individual genes were assessed as potential predictors of risk for progression. Conclusions: Tumor grade progression occurred with both high mutational homology and low mutational homology, which may represent both true tumor progression and de-novo growth. Validation of the identified tumor genes that appeared associated with progression may provide a clinically valuable tool to providers managing patients with LG urothelial carcinomas.

Original languageEnglish (US)
Pages (from-to)9415-9424
Number of pages10
JournalOncotarget
Volume9
Issue number10
DOIs
StatePublished - Jan 1 2018

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Urinary Bladder Neoplasms
Carcinoma
Neoplasms
Urinary Bladder
Genes
Exome
Germ-Line Mutation
Tertiary Care Centers
Databases

Keywords

  • Bladder cancer genomics
  • Low grade
  • Progression

ASJC Scopus subject areas

  • Oncology

Cite this

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title = "Grade progression in urothelial carcinoma can occur with high or low mutational homology: A first-step toward tumor-specific care in initial low-grade bladder cancer",
abstract = "Purpose: Low-grade (LG) urothelial carcinomas of the bladder (UCB) are common malignancies that are costly to surveil and rarely progress to life threatening, highgrade (HG) malignancies. It is unknown if the progression of LG to HG is a result of second primary tumors or transformation of existing LG tumors. We examined tumor genetics in patients with grade progression in urothelial carcinoma and compared to patients with no progression. Results: Five patients were identified with progression. Median time from initial LG diagnosis to HG diagnosis in those experiencing progression was 19 months. Progression with both high and low mutational homology was identified. Gene alterations associated with tumor grade progression in initial low grade tumors include FBN3, CIT and HECTD4. Materials and Methods: An institutional cancer database at a tertiary referral center in the United States identified patients who progressed from LG to HG UCB. Histologic re-review was performed by a genitourinary pathologist. Whole exome sequencing with correction for germline mutations by buffy coat subtraction was performed. Mutations were assessed between LG tumors and subsequent samepatient HG tumors and for LG patients who did not progress. Individual genes were assessed as potential predictors of risk for progression. Conclusions: Tumor grade progression occurred with both high mutational homology and low mutational homology, which may represent both true tumor progression and de-novo growth. Validation of the identified tumor genes that appeared associated with progression may provide a clinically valuable tool to providers managing patients with LG urothelial carcinomas.",
keywords = "Bladder cancer genomics, Low grade, Progression",
author = "Ralf Kittler and Christine Shiang and Hutchinson, {Ryan Craig} and Kollipara, {Rahul K.} and Payal Kapur and Franto Francis and Yair Lotan",
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T2 - A first-step toward tumor-specific care in initial low-grade bladder cancer

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AU - Shiang, Christine

AU - Hutchinson, Ryan Craig

AU - Kollipara, Rahul K.

AU - Kapur, Payal

AU - Francis, Franto

AU - Lotan, Yair

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N2 - Purpose: Low-grade (LG) urothelial carcinomas of the bladder (UCB) are common malignancies that are costly to surveil and rarely progress to life threatening, highgrade (HG) malignancies. It is unknown if the progression of LG to HG is a result of second primary tumors or transformation of existing LG tumors. We examined tumor genetics in patients with grade progression in urothelial carcinoma and compared to patients with no progression. Results: Five patients were identified with progression. Median time from initial LG diagnosis to HG diagnosis in those experiencing progression was 19 months. Progression with both high and low mutational homology was identified. Gene alterations associated with tumor grade progression in initial low grade tumors include FBN3, CIT and HECTD4. Materials and Methods: An institutional cancer database at a tertiary referral center in the United States identified patients who progressed from LG to HG UCB. Histologic re-review was performed by a genitourinary pathologist. Whole exome sequencing with correction for germline mutations by buffy coat subtraction was performed. Mutations were assessed between LG tumors and subsequent samepatient HG tumors and for LG patients who did not progress. Individual genes were assessed as potential predictors of risk for progression. Conclusions: Tumor grade progression occurred with both high mutational homology and low mutational homology, which may represent both true tumor progression and de-novo growth. Validation of the identified tumor genes that appeared associated with progression may provide a clinically valuable tool to providers managing patients with LG urothelial carcinomas.

AB - Purpose: Low-grade (LG) urothelial carcinomas of the bladder (UCB) are common malignancies that are costly to surveil and rarely progress to life threatening, highgrade (HG) malignancies. It is unknown if the progression of LG to HG is a result of second primary tumors or transformation of existing LG tumors. We examined tumor genetics in patients with grade progression in urothelial carcinoma and compared to patients with no progression. Results: Five patients were identified with progression. Median time from initial LG diagnosis to HG diagnosis in those experiencing progression was 19 months. Progression with both high and low mutational homology was identified. Gene alterations associated with tumor grade progression in initial low grade tumors include FBN3, CIT and HECTD4. Materials and Methods: An institutional cancer database at a tertiary referral center in the United States identified patients who progressed from LG to HG UCB. Histologic re-review was performed by a genitourinary pathologist. Whole exome sequencing with correction for germline mutations by buffy coat subtraction was performed. Mutations were assessed between LG tumors and subsequent samepatient HG tumors and for LG patients who did not progress. Individual genes were assessed as potential predictors of risk for progression. Conclusions: Tumor grade progression occurred with both high mutational homology and low mutational homology, which may represent both true tumor progression and de-novo growth. Validation of the identified tumor genes that appeared associated with progression may provide a clinically valuable tool to providers managing patients with LG urothelial carcinomas.

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