An epigenetic marker panel for recurrence risk prediction of low grade papillary urothelial cell carcinoma (LGPUCC) and its potential use for surveillance after transurethral resection using urine

Leonel Maldonado, Mariana Brait, Christina Michailidi, Enrico Munari, Tina Driscoll, Luciana Schultz, Trinity Bivalacqua, Mark P. Schoenberg, David Sidransky, George J. Netto, Mohammad Obaidul Hoque

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

By a candidate gene approach, we analyzed the promoter methylation (PM) of 8 genes (ARF, TIMP3, RAR-β2, NID2, CCNA1, AIM1, CALCA and CCND2) by quantitative methylation specific PCR (QMSP) in the DNA of 17 non-recurrent and 19 recurrent noninvasive low grade papillary urothelial cell carcinoma (LGPUCC) archival tissues. Among the genes tested, by establishing an empiric cutoff value, CCND2, CCNA1, NID2, and CALCA showed higher frequency of methylation in recurrent than in non-recurrent LGPUCC: CCND2 10/19 (53%) vs. 2/17 (12%) (p=0.014); CCNA1 11/19 (58%) vs. 4/17 (23.5%) (p=0.048); NID2 13/19 (68%) vs. 3/17 (18%) (p=0.003) and CALCA 10/19 (53%) vs. 4/17 (23.5%) (p=0.097), respectively. We further analyzed PM of CCND2, CCNA1, and CALCA in urine DNA from UCC patients including LGPUCC and controls. The frequency of CCND2, CCNA1, and CALCA was significantly higher (p<0.0001) in urine of UCC cases [38/148 (26%), 50/73 (68%) and 94/148 (63.5%) respectively] than controls [0/56 (0%), 10/60 (17%) and 16/56 (28.5%), respectively)]. Most importantly we found at least one of the 3 markers were methylated positive in 25 out of 30 (83%) cytology negative LGPUCC cases. We also explored the biological function of CCNA1 in UCC. Prospective confirmatory studies are needed to develop a reliable tool for prediction of recurrence using primary LGPUCC tissues and/or urine.

Original languageEnglish (US)
Pages (from-to)5218-5233
Number of pages16
JournalOncotarget
Volume5
Issue number14
StatePublished - 2014
Externally publishedYes

Fingerprint

Epigenomics
Methylation
Urine
Carcinoma
Recurrence
Genes
DNA
Cell Biology
Prospective Studies
Polymerase Chain Reaction

Keywords

  • Biomarkers
  • DNA methylation
  • Epigenetics
  • LGPUCC
  • Recurrence

ASJC Scopus subject areas

  • Oncology

Cite this

An epigenetic marker panel for recurrence risk prediction of low grade papillary urothelial cell carcinoma (LGPUCC) and its potential use for surveillance after transurethral resection using urine. / Maldonado, Leonel; Brait, Mariana; Michailidi, Christina; Munari, Enrico; Driscoll, Tina; Schultz, Luciana; Bivalacqua, Trinity; Schoenberg, Mark P.; Sidransky, David; Netto, George J.; Hoque, Mohammad Obaidul.

In: Oncotarget, Vol. 5, No. 14, 2014, p. 5218-5233.

Research output: Contribution to journalArticle

Maldonado, L, Brait, M, Michailidi, C, Munari, E, Driscoll, T, Schultz, L, Bivalacqua, T, Schoenberg, MP, Sidransky, D, Netto, GJ & Hoque, MO 2014, 'An epigenetic marker panel for recurrence risk prediction of low grade papillary urothelial cell carcinoma (LGPUCC) and its potential use for surveillance after transurethral resection using urine', Oncotarget, vol. 5, no. 14, pp. 5218-5233.
Maldonado, Leonel ; Brait, Mariana ; Michailidi, Christina ; Munari, Enrico ; Driscoll, Tina ; Schultz, Luciana ; Bivalacqua, Trinity ; Schoenberg, Mark P. ; Sidransky, David ; Netto, George J. ; Hoque, Mohammad Obaidul. / An epigenetic marker panel for recurrence risk prediction of low grade papillary urothelial cell carcinoma (LGPUCC) and its potential use for surveillance after transurethral resection using urine. In: Oncotarget. 2014 ; Vol. 5, No. 14. pp. 5218-5233.
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abstract = "By a candidate gene approach, we analyzed the promoter methylation (PM) of 8 genes (ARF, TIMP3, RAR-β2, NID2, CCNA1, AIM1, CALCA and CCND2) by quantitative methylation specific PCR (QMSP) in the DNA of 17 non-recurrent and 19 recurrent noninvasive low grade papillary urothelial cell carcinoma (LGPUCC) archival tissues. Among the genes tested, by establishing an empiric cutoff value, CCND2, CCNA1, NID2, and CALCA showed higher frequency of methylation in recurrent than in non-recurrent LGPUCC: CCND2 10/19 (53{\%}) vs. 2/17 (12{\%}) (p=0.014); CCNA1 11/19 (58{\%}) vs. 4/17 (23.5{\%}) (p=0.048); NID2 13/19 (68{\%}) vs. 3/17 (18{\%}) (p=0.003) and CALCA 10/19 (53{\%}) vs. 4/17 (23.5{\%}) (p=0.097), respectively. We further analyzed PM of CCND2, CCNA1, and CALCA in urine DNA from UCC patients including LGPUCC and controls. The frequency of CCND2, CCNA1, and CALCA was significantly higher (p<0.0001) in urine of UCC cases [38/148 (26{\%}), 50/73 (68{\%}) and 94/148 (63.5{\%}) respectively] than controls [0/56 (0{\%}), 10/60 (17{\%}) and 16/56 (28.5{\%}), respectively)]. Most importantly we found at least one of the 3 markers were methylated positive in 25 out of 30 (83{\%}) cytology negative LGPUCC cases. We also explored the biological function of CCNA1 in UCC. Prospective confirmatory studies are needed to develop a reliable tool for prediction of recurrence using primary LGPUCC tissues and/or urine.",
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T1 - An epigenetic marker panel for recurrence risk prediction of low grade papillary urothelial cell carcinoma (LGPUCC) and its potential use for surveillance after transurethral resection using urine

AU - Maldonado, Leonel

AU - Brait, Mariana

AU - Michailidi, Christina

AU - Munari, Enrico

AU - Driscoll, Tina

AU - Schultz, Luciana

AU - Bivalacqua, Trinity

AU - Schoenberg, Mark P.

AU - Sidransky, David

AU - Netto, George J.

AU - Hoque, Mohammad Obaidul

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