Genomic landscape of inverted urothelial papilloma and urothelial papilloma of the bladder

Sumit Isharwal, Wenhuo Hu, Judy Sarungbam, Ying bei Chen, Anuradha Gopalan, Samson W. Fine, Satish K. Tickoo, Sahussapont J. Sirintrapun, Sana Jadallah, Florence L. Loo, Eugene J. Pietzak, Eugene K. Cha, Bernard H. Bochner, Michael F. Berger, Gopa Iyer, David B. Solit, Victor E. Reuter, Hikmat Al-Ahmadie

Research output: Contribution to journalArticle

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Abstract

Inverted urothelial papilloma (IUP) and urothelial papilloma (UP) are rare urothelial neoplasms that typically follow a benign clinical course. Oncogenic mutations in FGFR3, HRAS, and the TERT promoter have been reported in these entities but no comprehensive molecular analysis has been performed. We sought to characterize the genomic landscape of IUP and UP using whole-exome and targeted next-generation sequencing. In IUP, 10 of 11 tumors harbored oncogenic hotspot mutations in HRAS and the remaining tumor had an oncogenic KRAS mutation. None of the IUP tumors harbored TERT promoter or FGFR3 mutations. In UP, 8 of 11 tumors had oncogenic KRAS mutations and two had oncogenic HRAS mutations. One UP tumor had oncogenic mutations in FGFR3, PIK3CA, and the TERT promoter, and arose in a patient with recurrent non-invasive papillary urothelial carcinomas. In contrast to urothelial carcinoma, the APOBEC mutational signature was not present in any IUP and UP tumors, and oncogenic alterations in chromatin remodeling genes were uncommon in both IUP and UP. The current study suggests that IUP and UP are driven primarily by RAS pathway activation and lack the more common genomic features of urothelial cancers.

Original languageEnglish (US)
JournalJournal of Pathology
DOIs
StatePublished - Jan 1 2019

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Inverted Papilloma
Papilloma
Urinary Bladder
Mutation
Neoplasms
Exome
Chromatin Assembly and Disassembly
Papillary Carcinoma
Carcinoma

Keywords

  • genomics
  • inverted urothelial papilloma
  • RAS pathway
  • urothelial carcinoma
  • urothelial papilloma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Genomic landscape of inverted urothelial papilloma and urothelial papilloma of the bladder. / Isharwal, Sumit; Hu, Wenhuo; Sarungbam, Judy; Chen, Ying bei; Gopalan, Anuradha; Fine, Samson W.; Tickoo, Satish K.; Sirintrapun, Sahussapont J.; Jadallah, Sana; Loo, Florence L.; Pietzak, Eugene J.; Cha, Eugene K.; Bochner, Bernard H.; Berger, Michael F.; Iyer, Gopa; Solit, David B.; Reuter, Victor E.; Al-Ahmadie, Hikmat.

In: Journal of Pathology, 01.01.2019.

Research output: Contribution to journalArticle

Isharwal, S, Hu, W, Sarungbam, J, Chen, YB, Gopalan, A, Fine, SW, Tickoo, SK, Sirintrapun, SJ, Jadallah, S, Loo, FL, Pietzak, EJ, Cha, EK, Bochner, BH, Berger, MF, Iyer, G, Solit, DB, Reuter, VE & Al-Ahmadie, H 2019, 'Genomic landscape of inverted urothelial papilloma and urothelial papilloma of the bladder', Journal of Pathology. https://doi.org/10.1002/path.5261
Isharwal, Sumit ; Hu, Wenhuo ; Sarungbam, Judy ; Chen, Ying bei ; Gopalan, Anuradha ; Fine, Samson W. ; Tickoo, Satish K. ; Sirintrapun, Sahussapont J. ; Jadallah, Sana ; Loo, Florence L. ; Pietzak, Eugene J. ; Cha, Eugene K. ; Bochner, Bernard H. ; Berger, Michael F. ; Iyer, Gopa ; Solit, David B. ; Reuter, Victor E. ; Al-Ahmadie, Hikmat. / Genomic landscape of inverted urothelial papilloma and urothelial papilloma of the bladder. In: Journal of Pathology. 2019.
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AU - Gopalan, Anuradha

AU - Fine, Samson W.

AU - Tickoo, Satish K.

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AU - Cha, Eugene K.

AU - Bochner, Bernard H.

AU - Berger, Michael F.

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AU - Al-Ahmadie, Hikmat

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