Tumor evolution and progression in multifocal and paired non-invasive/invasive urothelial carcinoma

Joshua Warrick, Daniel H. Hovelson, Anmol Amin, Chia Jen Liu, Andi K. Cani, Andrew S. McDaniel, Venkata Yadati, Michael J. Quist, Alon Z. Weizer, J. Chad Brenner, Felix Y. Feng, Rohit Mehra, Catherine S. Grasso, Scott A. Tomlins

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Although multifocal tumors and non-invasive/invasive components are commonly encountered in surgical pathology, their genetic relationship is often poorly characterized. We used next-generation sequencing (NGS) to characterize somatic alterations in a patient with five spatially distinct, high-grade papillary urothelial carcinomas (UCs), with one tumor harboring an underlying invasive component. NGS of 409 cancer-related genes was performed on DNA isolated from formalin-fixed paraffin-embedded (FFPE) blocks representing each papillary tumor (n = 5), the invasive component of one tumor, and matched normal tissue. We identified nine unique non-synonymous somatic mutations across the six UC samples, including five present in each carcinoma sample, consistent with clonal origin and limited intertumoral heterogeneity. Copy number and loss of heterogeneity (LOH) profiles were similar in all six carcinomas; however, the invasive carcinoma component uniquely showed focal CDKN2A loss and chromosome 9 LOH and did not harbor gains of chromosomes 5p or X that were present in the other tumor samples. Phylogenetic analysis supported the invasive component arising from a shared progenitor prior to the outgrowth of cells in the non-invasive tumors. Results were extended to three additional cases of upper tract UC with paired non-invasive/invasive components, which identified driving alterations exclusive to both non-invasive and invasive components. Lastly, we performed targeted RNA sequencing (RNAseq) using a custom bladder cancer panel, which confirmed gene expression signature differences between paired non-invasive/invasive components. The results and approaches presented here may be useful in understanding the clonal relationships in multifocal cancers or paired non-invasive/invasive components from routine FFPE specimens.

Original languageEnglish (US)
Pages (from-to)297-311
Number of pages15
JournalVirchows Archiv
Volume466
Issue number3
DOIs
StatePublished - Mar 10 2015

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Carcinoma
Neoplasms
Paraffin
Formaldehyde
RNA Sequence Analysis
Surgical Pathology
Chromosomes, Human, Pair 9
Papillary Carcinoma
Neoplasm Genes
Transcriptome
Urinary Bladder Neoplasms
Chromosomes
Mutation
DNA

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Warrick, J., Hovelson, D. H., Amin, A., Liu, C. J., Cani, A. K., McDaniel, A. S., ... Tomlins, S. A. (2015). Tumor evolution and progression in multifocal and paired non-invasive/invasive urothelial carcinoma. Virchows Archiv, 466(3), 297-311. https://doi.org/10.1007/s00428-014-1699-y
Warrick, Joshua ; Hovelson, Daniel H. ; Amin, Anmol ; Liu, Chia Jen ; Cani, Andi K. ; McDaniel, Andrew S. ; Yadati, Venkata ; Quist, Michael J. ; Weizer, Alon Z. ; Brenner, J. Chad ; Feng, Felix Y. ; Mehra, Rohit ; Grasso, Catherine S. ; Tomlins, Scott A. / Tumor evolution and progression in multifocal and paired non-invasive/invasive urothelial carcinoma. In: Virchows Archiv. 2015 ; Vol. 466, No. 3. pp. 297-311.
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Warrick, J, Hovelson, DH, Amin, A, Liu, CJ, Cani, AK, McDaniel, AS, Yadati, V, Quist, MJ, Weizer, AZ, Brenner, JC, Feng, FY, Mehra, R, Grasso, CS & Tomlins, SA 2015, 'Tumor evolution and progression in multifocal and paired non-invasive/invasive urothelial carcinoma', Virchows Archiv, vol. 466, no. 3, pp. 297-311. https://doi.org/10.1007/s00428-014-1699-y

Tumor evolution and progression in multifocal and paired non-invasive/invasive urothelial carcinoma. / Warrick, Joshua; Hovelson, Daniel H.; Amin, Anmol; Liu, Chia Jen; Cani, Andi K.; McDaniel, Andrew S.; Yadati, Venkata; Quist, Michael J.; Weizer, Alon Z.; Brenner, J. Chad; Feng, Felix Y.; Mehra, Rohit; Grasso, Catherine S.; Tomlins, Scott A.

In: Virchows Archiv, Vol. 466, No. 3, 10.03.2015, p. 297-311.

Research output: Contribution to journalArticle

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T1 - Tumor evolution and progression in multifocal and paired non-invasive/invasive urothelial carcinoma

AU - Warrick, Joshua

AU - Hovelson, Daniel H.

AU - Amin, Anmol

AU - Liu, Chia Jen

AU - Cani, Andi K.

AU - McDaniel, Andrew S.

AU - Yadati, Venkata

AU - Quist, Michael J.

AU - Weizer, Alon Z.

AU - Brenner, J. Chad

AU - Feng, Felix Y.

AU - Mehra, Rohit

AU - Grasso, Catherine S.

AU - Tomlins, Scott A.

PY - 2015/3/10

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