ERG and CHD1 heterogeneity in prostate cancer: Use of confocal microscopy in assessment of microscopic foci. Issue 15 (29th August 2014)

• Record Type: Journal Article
• Authors: Tereshchenko, Irina V.; Zhong, Hua; Chekmareva, Marina A.; Kane‐Goldsmith, Noriko; Santanam, Urmila; Petrosky, Whitney; Stein, Mark N.; Ganesan, Shridar; Singer, Eric A.; Moore, Dirk; Tischfield, Jay A.; DiPaola, Robert S.
• Is Part Of: Prostate. Volume 74:Issue 15(2014)
• Page Start: 1551
• Page End: 1559
• Publication Date: 2014-08-29
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.22873
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pros22873-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>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.</p> </sec> <sec id="pros22873-sec-0002" sec-type="section"> <title>METHODS</title> <p>Using confocal microscopy to identify cell‐to‐cell relationships in situ, we studied the most common gene rearrangement in prostate cancer (<italic>TMPRSS2</italic> and <italic>ERG</italic>) and the tumor suppressor <italic>CHD1</italic> in 56 patients who underwent radical prostatectomy.</p> </sec> <sec id="pros22873-sec-0003" sec-type="section"> <title>RESULTS</title> <p>Wild type <italic>ERG</italic> was found in 22 of 56 patients; <italic>ERG</italic> copy number was increased in 10/56, and <italic>ERG</italic> rearrangements confirmed in 24/56 patients. In 24 patients with <italic>ERG</italic> 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 <italic>CHD1</italic> deletion, with the majority of patients with <italic>CHD1</italic> deletions (13/14) correlating with <italic>ERG</italic>‐rearrangement negative status (<italic>P</italic> < 0.001).</p> </sec> <sec id="pros22873-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>These results demonstrate the ability of confocal microscopy and FISH to identify the cell‐to‐cell differences in common gene fusions such as <italic>TMPRSS2–ERG</italic> 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. <italic>Prostate 74:1551–1559, 2014</italic>. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>