A fluorescence in situ hybridization screen for E26 transformation-specific aberrations: Identification of DDX5-ETV4 fusion protein in prostate cancer

Bo Han, Rohit Mehra, Saravana M. Dhanasekaran, Jindan Yu, Anjana Menon, Robert J. Lonigro, Xiaosong Wang, Yusong Gong, Lei Wang, Sunita Shankar, Bharathi Laxman, Rajal B. Shah, Sooryanarayana Varambally, Nallasivam Palanisamy, Scott A. Tomlins, Chandan Kumar-Sinha, Arul M. Chinnaiyan

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Abstract

Recurrent gene fusions involving E26 transformation-specific (ETS) transcription factors ERG, ETV1, ETV4, or ETV5 have been identified in 40% to 70% of prostate cancers. Here, we used a comprehensive fluorescence in situ hybridization (FISH) split probe strategy interrogating all 27 ETS family members and their five known 5′ fusion partners in a cohort of 110 clinically localized prostate cancer patients. Gene rearrangements were only identified in ETS genes that were previously implicated in prostate cancer gene fusions including ERG, ETV1, and ETV4 (43%, 5%, and 5%, respectively), suggesting that a substantial fraction of prostate cancers (estimated at 30-60%) cannot be attributed to an ETS gene fusion. Among the known 5′ gene fusion partners, TMPRSS2 was rearranged in 47% of cases followed by SLC45A3, HNRPA2B1, and C15ORF21 in 2%, 1%, and 1% of cases, respectively. Based on this comprehensive FISH screen, we have made four note-worthy observations. First, by screening the entire ETS transcription factor family for rearrangements, we found that a large fraction of prostate cancers (44%) cannot be ascribed to an ETS gene fusion, an observation which will stimulate research into identifying recurrent non-ETS aberrations in prostate cancers. Second, we identified SLC45A3 as a novel 5′ fusion partner of ERG; previously, TMPRSS2 was the only described 5′ partner of ERG. Third, we identified two prostate-specific, androgen-induced genes, FLJ35294 and CANT1, as 5′ partners to ETV1 and ETV4. Fourth, we identified a ubiquitously expressed, androgen-insensitive gene, DDX5, fused in frame with ETV4, leading to the expression of a DDX5-ETV4 fusion protein.

Original languageEnglish (US)
Pages (from-to)7629-7637
Number of pages9
JournalCancer Research
Volume68
Issue number18
DOIs
StatePublished - Sep 15 2008
Externally publishedYes

Fingerprint

Fluorescence In Situ Hybridization
Gene Fusion
Prostatic Neoplasms
Proteins
Androgens
Transcription Factors
Genes
Gene Rearrangement
Neoplasm Genes
Prostate
Observation
Research

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A fluorescence in situ hybridization screen for E26 transformation-specific aberrations : Identification of DDX5-ETV4 fusion protein in prostate cancer. / Han, Bo; Mehra, Rohit; Dhanasekaran, Saravana M.; Yu, Jindan; Menon, Anjana; Lonigro, Robert J.; Wang, Xiaosong; Gong, Yusong; Wang, Lei; Shankar, Sunita; Laxman, Bharathi; Shah, Rajal B.; Varambally, Sooryanarayana; Palanisamy, Nallasivam; Tomlins, Scott A.; Kumar-Sinha, Chandan; Chinnaiyan, Arul M.

In: Cancer Research, Vol. 68, No. 18, 15.09.2008, p. 7629-7637.

Research output: Contribution to journalArticle

Han, B, Mehra, R, Dhanasekaran, SM, Yu, J, Menon, A, Lonigro, RJ, Wang, X, Gong, Y, Wang, L, Shankar, S, Laxman, B, Shah, RB, Varambally, S, Palanisamy, N, Tomlins, SA, Kumar-Sinha, C & Chinnaiyan, AM 2008, 'A fluorescence in situ hybridization screen for E26 transformation-specific aberrations: Identification of DDX5-ETV4 fusion protein in prostate cancer', Cancer Research, vol. 68, no. 18, pp. 7629-7637. https://doi.org/10.1158/0008-5472.CAN-08-2014
Han, Bo ; Mehra, Rohit ; Dhanasekaran, Saravana M. ; Yu, Jindan ; Menon, Anjana ; Lonigro, Robert J. ; Wang, Xiaosong ; Gong, Yusong ; Wang, Lei ; Shankar, Sunita ; Laxman, Bharathi ; Shah, Rajal B. ; Varambally, Sooryanarayana ; Palanisamy, Nallasivam ; Tomlins, Scott A. ; Kumar-Sinha, Chandan ; Chinnaiyan, Arul M. / A fluorescence in situ hybridization screen for E26 transformation-specific aberrations : Identification of DDX5-ETV4 fusion protein in prostate cancer. In: Cancer Research. 2008 ; Vol. 68, No. 18. pp. 7629-7637.
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abstract = "Recurrent gene fusions involving E26 transformation-specific (ETS) transcription factors ERG, ETV1, ETV4, or ETV5 have been identified in 40{\%} to 70{\%} of prostate cancers. Here, we used a comprehensive fluorescence in situ hybridization (FISH) split probe strategy interrogating all 27 ETS family members and their five known 5′ fusion partners in a cohort of 110 clinically localized prostate cancer patients. Gene rearrangements were only identified in ETS genes that were previously implicated in prostate cancer gene fusions including ERG, ETV1, and ETV4 (43{\%}, 5{\%}, and 5{\%}, respectively), suggesting that a substantial fraction of prostate cancers (estimated at 30-60{\%}) cannot be attributed to an ETS gene fusion. Among the known 5′ gene fusion partners, TMPRSS2 was rearranged in 47{\%} of cases followed by SLC45A3, HNRPA2B1, and C15ORF21 in 2{\%}, 1{\%}, and 1{\%} of cases, respectively. Based on this comprehensive FISH screen, we have made four note-worthy observations. First, by screening the entire ETS transcription factor family for rearrangements, we found that a large fraction of prostate cancers (44{\%}) cannot be ascribed to an ETS gene fusion, an observation which will stimulate research into identifying recurrent non-ETS aberrations in prostate cancers. Second, we identified SLC45A3 as a novel 5′ fusion partner of ERG; previously, TMPRSS2 was the only described 5′ partner of ERG. Third, we identified two prostate-specific, androgen-induced genes, FLJ35294 and CANT1, as 5′ partners to ETV1 and ETV4. Fourth, we identified a ubiquitously expressed, androgen-insensitive gene, DDX5, fused in frame with ETV4, leading to the expression of a DDX5-ETV4 fusion protein.",
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AU - Mehra, Rohit

AU - Dhanasekaran, Saravana M.

AU - Yu, Jindan

AU - Menon, Anjana

AU - Lonigro, Robert J.

AU - Wang, Xiaosong

AU - Gong, Yusong

AU - Wang, Lei

AU - Shankar, Sunita

AU - Laxman, Bharathi

AU - Shah, Rajal B.

AU - Varambally, Sooryanarayana

AU - Palanisamy, Nallasivam

AU - Tomlins, Scott A.

AU - Kumar-Sinha, Chandan

AU - Chinnaiyan, Arul M.

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