Prevalence of chromosomal rearrangements involving non-ETS genes in prostate cancer

Martina Kluth; Rami Galal; Antje Krohn; Joachim Weischenfeldt; Christina Tsourlakis; Lisa Paustian; Ramin Ahrary; Malik Ahmed; Sekander Scherzai; Anne Meyer; Hüseyin Sirma; Jan Korbel; Guido Sauter; Thorsten Schlomm; Ronald Simon; Sarah Minner

doi:10.3892/ijo.2015.2855

Prevalence of chromosomal rearrangements involving non-ETS genes in prostate cancer

Martina Kluth, Rami Galal, Antje Krohn, Joachim Weischenfeldt, Christina Tsourlakis, Lisa Paustian, Ramin Ahrary, Malik Ahmed, Sekander Scherzai, Anne Meyer, Hüseyin Sirma, Jan Korbel, Guido Sauter, Thorsten Schlomm, Ronald Simon, Sarah Minner

8 Citations (Scopus)

Abstract

Prostate cancer is characterized by structural rearrangements, most frequently including translocations between androgen-dependent genes and members of the ETS family of transcription factor like TMPRSS2:ERG. In a recent whole genome sequencing study we identified 140 gene fusions that were unrelated to ETS genes in 11 prostate cancers. The aim of the present study was to estimate the prevalence of non-ETS gene fusions. We randomly selected 27 of these rearrangements and analyzed them by fluorescence in situ hybridization (FISH) in a tissue microarray format containing 500 prostate cancers. Using break-apart FISH probes for one fusion partner each, we found rearrangements of 13 (48%) of the 27 analyzed genes in 300-400 analyzable cancers per gene. Recurrent breakage, often accompanied by partial deletion of the genes, was found for NCKAP5, SH3BGR and TTC3 in 3 (0.8%) tumors each, as well as for ARNTL2 and ENOX1 in 2 (0.5%) cancers each. One rearranged tumor sample was observed for each of VCL, ZNF578, IMMP2L, SLC16A12, PANK1, GPHN, LRP1 and ZHX2. Balanced rearrangements, indicating possible gene fusion, were found for ZNF578, SH3BGR, LPR12 and ZHX2 in individual cancers only. The results of the present study confirm that rearrangements involving non-ETS genes occur in prostate cancer, but demonstrate that they are highly individual and typically non-recurrent.

Original language	English
Journal	International Journal of Oncology
Volume	46
Issue number	4
Pages (from-to)	1637-42
Number of pages	6
ISSN	1019-6439
DOIs	https://doi.org/10.3892/ijo.2015.2855
Publication status	Published - 1 Apr 2015
Externally published	Yes

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Kluth, M., Galal, R., Krohn, A., Weischenfeldt, J., Tsourlakis, C., Paustian, L., Ahrary, R., Ahmed, M., Scherzai, S., Meyer, A., Sirma, H., Korbel, J., Sauter, G., Schlomm, T., Simon, R., & Minner, S. (2015). Prevalence of chromosomal rearrangements involving non-ETS genes in prostate cancer. International Journal of Oncology, 46(4), 1637-42. https://doi.org/10.3892/ijo.2015.2855

Kluth, M, Galal, R, Krohn, A, Weischenfeldt, J, Tsourlakis, C, Paustian, L, Ahrary, R, Ahmed, M, Scherzai, S, Meyer, A, Sirma, H, Korbel, J, Sauter, G, Schlomm, T, Simon, R & Minner, S 2015, 'Prevalence of chromosomal rearrangements involving non-ETS genes in prostate cancer', International Journal of Oncology, vol. 46, no. 4, pp. 1637-42. https://doi.org/10.3892/ijo.2015.2855

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abstract = "Prostate cancer is characterized by structural rearrangements, most frequently including translocations between androgen-dependent genes and members of the ETS family of transcription factor like TMPRSS2:ERG. In a recent whole genome sequencing study we identified 140 gene fusions that were unrelated to ETS genes in 11 prostate cancers. The aim of the present study was to estimate the prevalence of non-ETS gene fusions. We randomly selected 27 of these rearrangements and analyzed them by fluorescence in situ hybridization (FISH) in a tissue microarray format containing 500 prostate cancers. Using break-apart FISH probes for one fusion partner each, we found rearrangements of 13 (48%) of the 27 analyzed genes in 300-400 analyzable cancers per gene. Recurrent breakage, often accompanied by partial deletion of the genes, was found for NCKAP5, SH3BGR and TTC3 in 3 (0.8%) tumors each, as well as for ARNTL2 and ENOX1 in 2 (0.5%) cancers each. One rearranged tumor sample was observed for each of VCL, ZNF578, IMMP2L, SLC16A12, PANK1, GPHN, LRP1 and ZHX2. Balanced rearrangements, indicating possible gene fusion, were found for ZNF578, SH3BGR, LPR12 and ZHX2 in individual cancers only. The results of the present study confirm that rearrangements involving non-ETS genes occur in prostate cancer, but demonstrate that they are highly individual and typically non-recurrent.",

author = "Martina Kluth and Rami Galal and Antje Krohn and Joachim Weischenfeldt and Christina Tsourlakis and Lisa Paustian and Ramin Ahrary and Malik Ahmed and Sekander Scherzai and Anne Meyer and H{\"u}seyin Sirma and Jan Korbel and Guido Sauter and Thorsten Schlomm and Ronald Simon and Sarah Minner",

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AU - Kluth, Martina

AU - Galal, Rami

AU - Krohn, Antje

AU - Weischenfeldt, Joachim

AU - Tsourlakis, Christina

AU - Paustian, Lisa

AU - Ahrary, Ramin

AU - Ahmed, Malik

AU - Scherzai, Sekander

AU - Meyer, Anne

AU - Sirma, Hüseyin

AU - Korbel, Jan

AU - Sauter, Guido

AU - Schlomm, Thorsten

AU - Simon, Ronald

AU - Minner, Sarah

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Prostate cancer is characterized by structural rearrangements, most frequently including translocations between androgen-dependent genes and members of the ETS family of transcription factor like TMPRSS2:ERG. In a recent whole genome sequencing study we identified 140 gene fusions that were unrelated to ETS genes in 11 prostate cancers. The aim of the present study was to estimate the prevalence of non-ETS gene fusions. We randomly selected 27 of these rearrangements and analyzed them by fluorescence in situ hybridization (FISH) in a tissue microarray format containing 500 prostate cancers. Using break-apart FISH probes for one fusion partner each, we found rearrangements of 13 (48%) of the 27 analyzed genes in 300-400 analyzable cancers per gene. Recurrent breakage, often accompanied by partial deletion of the genes, was found for NCKAP5, SH3BGR and TTC3 in 3 (0.8%) tumors each, as well as for ARNTL2 and ENOX1 in 2 (0.5%) cancers each. One rearranged tumor sample was observed for each of VCL, ZNF578, IMMP2L, SLC16A12, PANK1, GPHN, LRP1 and ZHX2. Balanced rearrangements, indicating possible gene fusion, were found for ZNF578, SH3BGR, LPR12 and ZHX2 in individual cancers only. The results of the present study confirm that rearrangements involving non-ETS genes occur in prostate cancer, but demonstrate that they are highly individual and typically non-recurrent.

AB - Prostate cancer is characterized by structural rearrangements, most frequently including translocations between androgen-dependent genes and members of the ETS family of transcription factor like TMPRSS2:ERG. In a recent whole genome sequencing study we identified 140 gene fusions that were unrelated to ETS genes in 11 prostate cancers. The aim of the present study was to estimate the prevalence of non-ETS gene fusions. We randomly selected 27 of these rearrangements and analyzed them by fluorescence in situ hybridization (FISH) in a tissue microarray format containing 500 prostate cancers. Using break-apart FISH probes for one fusion partner each, we found rearrangements of 13 (48%) of the 27 analyzed genes in 300-400 analyzable cancers per gene. Recurrent breakage, often accompanied by partial deletion of the genes, was found for NCKAP5, SH3BGR and TTC3 in 3 (0.8%) tumors each, as well as for ARNTL2 and ENOX1 in 2 (0.5%) cancers each. One rearranged tumor sample was observed for each of VCL, ZNF578, IMMP2L, SLC16A12, PANK1, GPHN, LRP1 and ZHX2. Balanced rearrangements, indicating possible gene fusion, were found for ZNF578, SH3BGR, LPR12 and ZHX2 in individual cancers only. The results of the present study confirm that rearrangements involving non-ETS genes occur in prostate cancer, but demonstrate that they are highly individual and typically non-recurrent.

U2 - 10.3892/ijo.2015.2855

DO - 10.3892/ijo.2015.2855

M3 - Journal article

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SP - 1637

EP - 1642

JO - International Journal of Oncology

JF - International Journal of Oncology

IS - 4

ER -

Prevalence of chromosomal rearrangements involving non-ETS genes in prostate cancer

Abstract

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