Targeted sequencing of plasmacytoid urothelial carcinoma reveals frequent TERT promoter mutations

Doreen N. Palsgrove, Diana Taheri, Simeon U. Springer, Morgan Cowan, Gunes Guner, Maria A. Mendoza Rodriguez, Maria Del Carmen Rodriguez Pena, Yuxuan Wang, Isaac Kinde, Bernardo F.P. Ricardo, Isabela Cunha, Kazutoshi Fujita, Dilek Ertoy, Kenneth W Kinzler, Trinity Bivalacqua, Nickolas Papadopoulos, Bert Vogelstein, George J. Netto

Research output: Contribution to journalArticle

Abstract

Activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the most common genetic alterations in urothelial carcinoma (UC) of the bladder and upper urinary tract. Although the cadherin 1 (CDH1) gene is commonly mutated in the clinically aggressive plasmacytoid variant of urothelial carcinoma (PUC), little is known about their TERT promoter mutation status. A retrospective search of our archives for PUC and UC with plasmacytoid and/or signet ring cell features (2007-2014) was performed. Ten specimens from 10 patients had archived material available for DNA analysis and were included in the study. Intratumoral areas of nonplasmacytoid histology were also evaluated when present. Samples were analyzed for TERT promoter mutations with Safe-SeqS, a sequencing error-reduction technology, and sequenced using a targeted panel of the 10 most commonly mutated genes in bladder cancer on the Illumina MiSeq platform. TERT promoter mutations were detected in specimens with pure and focal plasmacytoid features (6/10). Similar to conventional UC, the predominant mutation identified was g.1295228C>T. In heterogeneous tumors with focal variant histology, concordant mutations were found in plasmacytoid and corresponding conventional, glandular, or sarcomatoid areas. Co-occurring mutations in tumor protein p53 (TP53, 2 cases) and kirsten rat sarcoma (KRAS) viral proto-oncogene (1 case) were also detected. TERT promoter mutations are frequently present in PUC, which provides further evidence that TERT promoter mutations are common events in bladder cancer, regardless of histologic subtype, and supports their inclusion in any liquid biopsy assay for bladder cancer.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalHuman Pathology
Volume85
DOIs
StatePublished - Mar 1 2019

Fingerprint

Telomerase
Carcinoma
Mutation
Urinary Bladder Neoplasms
Histology
Genes
Tumor Suppressor Protein p53
Proto-Oncogenes
Cadherins
Urinary Tract
Sarcoma
Neoplasms
Urinary Bladder
Technology
Biopsy
DNA

Keywords

  • Mutation
  • Plasmacytoid
  • PUC
  • Telomerase reverse transcriptase
  • TERT
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Palsgrove, D. N., Taheri, D., Springer, S. U., Cowan, M., Guner, G., Mendoza Rodriguez, M. A., ... Netto, G. J. (2019). Targeted sequencing of plasmacytoid urothelial carcinoma reveals frequent TERT promoter mutations. Human Pathology, 85, 1-9. https://doi.org/10.1016/j.humpath.2018.10.033

Targeted sequencing of plasmacytoid urothelial carcinoma reveals frequent TERT promoter mutations. / Palsgrove, Doreen N.; Taheri, Diana; Springer, Simeon U.; Cowan, Morgan; Guner, Gunes; Mendoza Rodriguez, Maria A.; Rodriguez Pena, Maria Del Carmen; Wang, Yuxuan; Kinde, Isaac; Ricardo, Bernardo F.P.; Cunha, Isabela; Fujita, Kazutoshi; Ertoy, Dilek; Kinzler, Kenneth W; Bivalacqua, Trinity; Papadopoulos, Nickolas; Vogelstein, Bert; Netto, George J.

In: Human Pathology, Vol. 85, 01.03.2019, p. 1-9.

Research output: Contribution to journalArticle

Palsgrove, DN, Taheri, D, Springer, SU, Cowan, M, Guner, G, Mendoza Rodriguez, MA, Rodriguez Pena, MDC, Wang, Y, Kinde, I, Ricardo, BFP, Cunha, I, Fujita, K, Ertoy, D, Kinzler, KW, Bivalacqua, T, Papadopoulos, N, Vogelstein, B & Netto, GJ 2019, 'Targeted sequencing of plasmacytoid urothelial carcinoma reveals frequent TERT promoter mutations', Human Pathology, vol. 85, pp. 1-9. https://doi.org/10.1016/j.humpath.2018.10.033
Palsgrove DN, Taheri D, Springer SU, Cowan M, Guner G, Mendoza Rodriguez MA et al. Targeted sequencing of plasmacytoid urothelial carcinoma reveals frequent TERT promoter mutations. Human Pathology. 2019 Mar 1;85:1-9. https://doi.org/10.1016/j.humpath.2018.10.033
Palsgrove, Doreen N. ; Taheri, Diana ; Springer, Simeon U. ; Cowan, Morgan ; Guner, Gunes ; Mendoza Rodriguez, Maria A. ; Rodriguez Pena, Maria Del Carmen ; Wang, Yuxuan ; Kinde, Isaac ; Ricardo, Bernardo F.P. ; Cunha, Isabela ; Fujita, Kazutoshi ; Ertoy, Dilek ; Kinzler, Kenneth W ; Bivalacqua, Trinity ; Papadopoulos, Nickolas ; Vogelstein, Bert ; Netto, George J. / Targeted sequencing of plasmacytoid urothelial carcinoma reveals frequent TERT promoter mutations. In: Human Pathology. 2019 ; Vol. 85. pp. 1-9.
@article{a55776b507684713aa54565ee3501618,
title = "Targeted sequencing of plasmacytoid urothelial carcinoma reveals frequent TERT promoter mutations",
abstract = "Activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the most common genetic alterations in urothelial carcinoma (UC) of the bladder and upper urinary tract. Although the cadherin 1 (CDH1) gene is commonly mutated in the clinically aggressive plasmacytoid variant of urothelial carcinoma (PUC), little is known about their TERT promoter mutation status. A retrospective search of our archives for PUC and UC with plasmacytoid and/or signet ring cell features (2007-2014) was performed. Ten specimens from 10 patients had archived material available for DNA analysis and were included in the study. Intratumoral areas of nonplasmacytoid histology were also evaluated when present. Samples were analyzed for TERT promoter mutations with Safe-SeqS, a sequencing error-reduction technology, and sequenced using a targeted panel of the 10 most commonly mutated genes in bladder cancer on the Illumina MiSeq platform. TERT promoter mutations were detected in specimens with pure and focal plasmacytoid features (6/10). Similar to conventional UC, the predominant mutation identified was g.1295228C>T. In heterogeneous tumors with focal variant histology, concordant mutations were found in plasmacytoid and corresponding conventional, glandular, or sarcomatoid areas. Co-occurring mutations in tumor protein p53 (TP53, 2 cases) and kirsten rat sarcoma (KRAS) viral proto-oncogene (1 case) were also detected. TERT promoter mutations are frequently present in PUC, which provides further evidence that TERT promoter mutations are common events in bladder cancer, regardless of histologic subtype, and supports their inclusion in any liquid biopsy assay for bladder cancer.",
keywords = "Mutation, Plasmacytoid, PUC, Telomerase reverse transcriptase, TERT, Urothelial carcinoma",
author = "Palsgrove, {Doreen N.} and Diana Taheri and Springer, {Simeon U.} and Morgan Cowan and Gunes Guner and {Mendoza Rodriguez}, {Maria A.} and {Rodriguez Pena}, {Maria Del Carmen} and Yuxuan Wang and Isaac Kinde and Ricardo, {Bernardo F.P.} and Isabela Cunha and Kazutoshi Fujita and Dilek Ertoy and Kinzler, {Kenneth W} and Trinity Bivalacqua and Nickolas Papadopoulos and Bert Vogelstein and Netto, {George J.}",
year = "2019",
month = "3",
day = "1",
doi = "10.1016/j.humpath.2018.10.033",
language = "English (US)",
volume = "85",
pages = "1--9",
journal = "Human Pathology",
issn = "0046-8177",
publisher = "W.B. Saunders Ltd",

}

TY - JOUR

T1 - Targeted sequencing of plasmacytoid urothelial carcinoma reveals frequent TERT promoter mutations

AU - Palsgrove, Doreen N.

AU - Taheri, Diana

AU - Springer, Simeon U.

AU - Cowan, Morgan

AU - Guner, Gunes

AU - Mendoza Rodriguez, Maria A.

AU - Rodriguez Pena, Maria Del Carmen

AU - Wang, Yuxuan

AU - Kinde, Isaac

AU - Ricardo, Bernardo F.P.

AU - Cunha, Isabela

AU - Fujita, Kazutoshi

AU - Ertoy, Dilek

AU - Kinzler, Kenneth W

AU - Bivalacqua, Trinity

AU - Papadopoulos, Nickolas

AU - Vogelstein, Bert

AU - Netto, George J.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the most common genetic alterations in urothelial carcinoma (UC) of the bladder and upper urinary tract. Although the cadherin 1 (CDH1) gene is commonly mutated in the clinically aggressive plasmacytoid variant of urothelial carcinoma (PUC), little is known about their TERT promoter mutation status. A retrospective search of our archives for PUC and UC with plasmacytoid and/or signet ring cell features (2007-2014) was performed. Ten specimens from 10 patients had archived material available for DNA analysis and were included in the study. Intratumoral areas of nonplasmacytoid histology were also evaluated when present. Samples were analyzed for TERT promoter mutations with Safe-SeqS, a sequencing error-reduction technology, and sequenced using a targeted panel of the 10 most commonly mutated genes in bladder cancer on the Illumina MiSeq platform. TERT promoter mutations were detected in specimens with pure and focal plasmacytoid features (6/10). Similar to conventional UC, the predominant mutation identified was g.1295228C>T. In heterogeneous tumors with focal variant histology, concordant mutations were found in plasmacytoid and corresponding conventional, glandular, or sarcomatoid areas. Co-occurring mutations in tumor protein p53 (TP53, 2 cases) and kirsten rat sarcoma (KRAS) viral proto-oncogene (1 case) were also detected. TERT promoter mutations are frequently present in PUC, which provides further evidence that TERT promoter mutations are common events in bladder cancer, regardless of histologic subtype, and supports their inclusion in any liquid biopsy assay for bladder cancer.

AB - Activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the most common genetic alterations in urothelial carcinoma (UC) of the bladder and upper urinary tract. Although the cadherin 1 (CDH1) gene is commonly mutated in the clinically aggressive plasmacytoid variant of urothelial carcinoma (PUC), little is known about their TERT promoter mutation status. A retrospective search of our archives for PUC and UC with plasmacytoid and/or signet ring cell features (2007-2014) was performed. Ten specimens from 10 patients had archived material available for DNA analysis and were included in the study. Intratumoral areas of nonplasmacytoid histology were also evaluated when present. Samples were analyzed for TERT promoter mutations with Safe-SeqS, a sequencing error-reduction technology, and sequenced using a targeted panel of the 10 most commonly mutated genes in bladder cancer on the Illumina MiSeq platform. TERT promoter mutations were detected in specimens with pure and focal plasmacytoid features (6/10). Similar to conventional UC, the predominant mutation identified was g.1295228C>T. In heterogeneous tumors with focal variant histology, concordant mutations were found in plasmacytoid and corresponding conventional, glandular, or sarcomatoid areas. Co-occurring mutations in tumor protein p53 (TP53, 2 cases) and kirsten rat sarcoma (KRAS) viral proto-oncogene (1 case) were also detected. TERT promoter mutations are frequently present in PUC, which provides further evidence that TERT promoter mutations are common events in bladder cancer, regardless of histologic subtype, and supports their inclusion in any liquid biopsy assay for bladder cancer.

KW - Mutation

KW - Plasmacytoid

KW - PUC

KW - Telomerase reverse transcriptase

KW - TERT

KW - Urothelial carcinoma

UR - http://www.scopus.com/inward/record.url?scp=85061042309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061042309&partnerID=8YFLogxK

U2 - 10.1016/j.humpath.2018.10.033

DO - 10.1016/j.humpath.2018.10.033

M3 - Article

VL - 85

SP - 1

EP - 9

JO - Human Pathology

JF - Human Pathology

SN - 0046-8177

ER -