ERG and CHDI heterogeneity in prostate cancer: Use of confocal microscopy in assessment of microscopic foci

Irina V. Tereshchenko, Hua Zhong, Marina A. Chekmareva, Noriko Kane-Goldsmith, Urmila Santanam, Whitney Petrosky, Mark Stein, Shridar Ganesan, Eric Singer, Dirk Moore, Jay Tischfield, Robert S. DiPaola

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

BACKGROUND. Biomarkers predicting tumor response are important to emerging targeted therapeutics. Complimentary methods to assess and understand genetic changes and heterogeneity within only few cancer cells in tissue will be a valuable addition for assessment of tumors such as prostate cancer that often have insufficient tumor for next generation sequencing in a single biopsy core. METHODS. Using confocal microscopy to identify cell-to-cell relationships in situ, we studied the most common gene rearrangement in prostate cancer (TMPRSS2 and ERG) and the tumor suppressor CHD1 in 56 patients who underwent radical prostatectomy. RESULTS. Wild type ERG was found in 22 of 56 patients; ERG copy number was increased in 10/56, and ERG rearrangements confirmed in 24/56 patients. In 24 patients with ERG rearrangements, the mechanisms of rearrangement were heterogeneous, with deletion in 14/24, a split event in 7/24, and both deletions and split events in the same tumor focus in 3/24 patients. Overall, 14/45 (31.1%) of patients had CHD1 deletion, with the majority of patients with CHD1 deletions (13/14) correlating with ERG-rearrangement negative status (P < 0.001). CONCLUSIONS. These results demonstrate the ability of confocal microscopy and FISH to identify the cell-to-cell differences in common gene fusions such as TMPRSS2-ERG that may arise independently within the same tumor focus. These data support the need to study complimentary approaches to assess genetic changes that may stratify therapy based on predicted sensitivities.

Original languageEnglish (US)
Pages (from-to)1551-1559
Number of pages9
JournalProstate
Volume74
Issue number15
DOIs
StatePublished - Nov 1 2014

Fingerprint

Confocal Microscopy
Prostatic Neoplasms
Neoplasms
Genetic Heterogeneity
Gene Rearrangement
Gene Fusion
Tumor Biomarkers
Prostatectomy
Biopsy
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology

Keywords

  • CHD1
  • Confocal microscopy
  • ERG
  • Heterogeneity
  • Prostate cancer
  • TMPRSS2

Cite this

Tereshchenko, I. V., Zhong, H., Chekmareva, M. A., Kane-Goldsmith, N., Santanam, U., Petrosky, W., ... DiPaola, R. S. (2014). ERG and CHDI heterogeneity in prostate cancer: Use of confocal microscopy in assessment of microscopic foci. Prostate, 74(15), 1551-1559. https://doi.org/10.1002/pros.22873
Tereshchenko, Irina V. ; Zhong, Hua ; Chekmareva, Marina A. ; Kane-Goldsmith, Noriko ; Santanam, Urmila ; Petrosky, Whitney ; Stein, Mark ; Ganesan, Shridar ; Singer, Eric ; Moore, Dirk ; Tischfield, Jay ; DiPaola, Robert S. / ERG and CHDI heterogeneity in prostate cancer : Use of confocal microscopy in assessment of microscopic foci. In: Prostate. 2014 ; Vol. 74, No. 15. pp. 1551-1559.
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abstract = "BACKGROUND. Biomarkers predicting tumor response are important to emerging targeted therapeutics. Complimentary methods to assess and understand genetic changes and heterogeneity within only few cancer cells in tissue will be a valuable addition for assessment of tumors such as prostate cancer that often have insufficient tumor for next generation sequencing in a single biopsy core. METHODS. Using confocal microscopy to identify cell-to-cell relationships in situ, we studied the most common gene rearrangement in prostate cancer (TMPRSS2 and ERG) and the tumor suppressor CHD1 in 56 patients who underwent radical prostatectomy. RESULTS. Wild type ERG was found in 22 of 56 patients; ERG copy number was increased in 10/56, and ERG rearrangements confirmed in 24/56 patients. In 24 patients with ERG rearrangements, the mechanisms of rearrangement were heterogeneous, with deletion in 14/24, a split event in 7/24, and both deletions and split events in the same tumor focus in 3/24 patients. Overall, 14/45 (31.1{\%}) of patients had CHD1 deletion, with the majority of patients with CHD1 deletions (13/14) correlating with ERG-rearrangement negative status (P < 0.001). CONCLUSIONS. These results demonstrate the ability of confocal microscopy and FISH to identify the cell-to-cell differences in common gene fusions such as TMPRSS2-ERG that may arise independently within the same tumor focus. These data support the need to study complimentary approaches to assess genetic changes that may stratify therapy based on predicted sensitivities.",
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Tereshchenko, IV, Zhong, H, Chekmareva, MA, Kane-Goldsmith, N, Santanam, U, Petrosky, W, Stein, M, Ganesan, S, Singer, E, Moore, D, Tischfield, J & DiPaola, RS 2014, 'ERG and CHDI heterogeneity in prostate cancer: Use of confocal microscopy in assessment of microscopic foci', Prostate, vol. 74, no. 15, pp. 1551-1559. https://doi.org/10.1002/pros.22873

ERG and CHDI heterogeneity in prostate cancer : Use of confocal microscopy in assessment of microscopic foci. / Tereshchenko, Irina V.; Zhong, Hua; Chekmareva, Marina A.; Kane-Goldsmith, Noriko; Santanam, Urmila; Petrosky, Whitney; Stein, Mark; Ganesan, Shridar; Singer, Eric; Moore, Dirk; Tischfield, Jay; DiPaola, Robert S.

In: Prostate, Vol. 74, No. 15, 01.11.2014, p. 1551-1559.

Research output: Contribution to journalArticle

TY - JOUR

T1 - ERG and CHDI heterogeneity in prostate cancer

T2 - Use of confocal microscopy in assessment of microscopic foci

AU - Tereshchenko, Irina V.

AU - Zhong, Hua

AU - Chekmareva, Marina A.

AU - Kane-Goldsmith, Noriko

AU - Santanam, Urmila

AU - Petrosky, Whitney

AU - Stein, Mark

AU - Ganesan, Shridar

AU - Singer, Eric

AU - Moore, Dirk

AU - Tischfield, Jay

AU - DiPaola, Robert S.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - BACKGROUND. Biomarkers predicting tumor response are important to emerging targeted therapeutics. Complimentary methods to assess and understand genetic changes and heterogeneity within only few cancer cells in tissue will be a valuable addition for assessment of tumors such as prostate cancer that often have insufficient tumor for next generation sequencing in a single biopsy core. METHODS. Using confocal microscopy to identify cell-to-cell relationships in situ, we studied the most common gene rearrangement in prostate cancer (TMPRSS2 and ERG) and the tumor suppressor CHD1 in 56 patients who underwent radical prostatectomy. RESULTS. Wild type ERG was found in 22 of 56 patients; ERG copy number was increased in 10/56, and ERG rearrangements confirmed in 24/56 patients. In 24 patients with ERG rearrangements, the mechanisms of rearrangement were heterogeneous, with deletion in 14/24, a split event in 7/24, and both deletions and split events in the same tumor focus in 3/24 patients. Overall, 14/45 (31.1%) of patients had CHD1 deletion, with the majority of patients with CHD1 deletions (13/14) correlating with ERG-rearrangement negative status (P < 0.001). CONCLUSIONS. These results demonstrate the ability of confocal microscopy and FISH to identify the cell-to-cell differences in common gene fusions such as TMPRSS2-ERG that may arise independently within the same tumor focus. These data support the need to study complimentary approaches to assess genetic changes that may stratify therapy based on predicted sensitivities.

AB - BACKGROUND. Biomarkers predicting tumor response are important to emerging targeted therapeutics. Complimentary methods to assess and understand genetic changes and heterogeneity within only few cancer cells in tissue will be a valuable addition for assessment of tumors such as prostate cancer that often have insufficient tumor for next generation sequencing in a single biopsy core. METHODS. Using confocal microscopy to identify cell-to-cell relationships in situ, we studied the most common gene rearrangement in prostate cancer (TMPRSS2 and ERG) and the tumor suppressor CHD1 in 56 patients who underwent radical prostatectomy. RESULTS. Wild type ERG was found in 22 of 56 patients; ERG copy number was increased in 10/56, and ERG rearrangements confirmed in 24/56 patients. In 24 patients with ERG rearrangements, the mechanisms of rearrangement were heterogeneous, with deletion in 14/24, a split event in 7/24, and both deletions and split events in the same tumor focus in 3/24 patients. Overall, 14/45 (31.1%) of patients had CHD1 deletion, with the majority of patients with CHD1 deletions (13/14) correlating with ERG-rearrangement negative status (P < 0.001). CONCLUSIONS. These results demonstrate the ability of confocal microscopy and FISH to identify the cell-to-cell differences in common gene fusions such as TMPRSS2-ERG that may arise independently within the same tumor focus. These data support the need to study complimentary approaches to assess genetic changes that may stratify therapy based on predicted sensitivities.

KW - CHD1

KW - Confocal microscopy

KW - ERG

KW - Heterogeneity

KW - Prostate cancer

KW - TMPRSS2

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DO - 10.1002/pros.22873

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Tereshchenko IV, Zhong H, Chekmareva MA, Kane-Goldsmith N, Santanam U, Petrosky W et al. ERG and CHDI heterogeneity in prostate cancer: Use of confocal microscopy in assessment of microscopic foci. Prostate. 2014 Nov 1;74(15):1551-1559. https://doi.org/10.1002/pros.22873