SPOP mutations in prostate cancer across demographically diverse patient cohorts

Mirjam Blattner, Daniel J. Lee, Catherine O'Reilly, Kyung Park, Theresa Y. MacDonald, Francesca Khani, Kevin Turner, Ya Lin Chiu, Peter J. Wild, Igor Dolgalev, Adriana Heguy, Andrea Sboner, Sinan Ramazangolu, Haley Hieronymus, Charles Sawyers, Ashutosh K. Tewari, Holger Moch, Ghil Suk Yoon, Yong Chul Known, Ove Andrén & 6 others Katja Fall, Francecsa Demichelis, Juan Miguel Mosquera, Brian D. Robinson, Christopher E. Barbieri, Mark A. Rubin

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Abstract

BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown. OBJECTIVE: To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material. DESIGN, SETTING, AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features. RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement (P < .01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1 deletions (P < .01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes. CONCLUSION: SPOP is mutated in 4.6% to 14.4% of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.

Original languageEnglish (US)
Pages (from-to)14-20
Number of pages7
JournalNeoplasia (United States)
Volume16
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

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Prostatic Neoplasms
Mutation
Proteins
Neoplasms
Mutant Proteins
Prostate-Specific Antigen
African Americans
Paraffin
Formaldehyde
Freezing
Population
Demography
Recurrence

ASJC Scopus subject areas

  • Cancer Research

Cite this

Blattner, M., Lee, D. J., O'Reilly, C., Park, K., MacDonald, T. Y., Khani, F., ... Rubin, M. A. (2014). SPOP mutations in prostate cancer across demographically diverse patient cohorts. Neoplasia (United States), 16(1), 14-20. https://doi.org/10.1593/neo.131704

SPOP mutations in prostate cancer across demographically diverse patient cohorts. / Blattner, Mirjam; Lee, Daniel J.; O'Reilly, Catherine; Park, Kyung; MacDonald, Theresa Y.; Khani, Francesca; Turner, Kevin; Chiu, Ya Lin; Wild, Peter J.; Dolgalev, Igor; Heguy, Adriana; Sboner, Andrea; Ramazangolu, Sinan; Hieronymus, Haley; Sawyers, Charles; Tewari, Ashutosh K.; Moch, Holger; Yoon, Ghil Suk; Known, Yong Chul; Andrén, Ove; Fall, Katja; Demichelis, Francecsa; Mosquera, Juan Miguel; Robinson, Brian D.; Barbieri, Christopher E.; Rubin, Mark A.

In: Neoplasia (United States), Vol. 16, No. 1, 2014, p. 14-20.

Research output: Contribution to journalArticle

Blattner, M, Lee, DJ, O'Reilly, C, Park, K, MacDonald, TY, Khani, F, Turner, K, Chiu, YL, Wild, PJ, Dolgalev, I, Heguy, A, Sboner, A, Ramazangolu, S, Hieronymus, H, Sawyers, C, Tewari, AK, Moch, H, Yoon, GS, Known, YC, Andrén, O, Fall, K, Demichelis, F, Mosquera, JM, Robinson, BD, Barbieri, CE & Rubin, MA 2014, 'SPOP mutations in prostate cancer across demographically diverse patient cohorts', Neoplasia (United States), vol. 16, no. 1, pp. 14-20. https://doi.org/10.1593/neo.131704
Blattner, Mirjam ; Lee, Daniel J. ; O'Reilly, Catherine ; Park, Kyung ; MacDonald, Theresa Y. ; Khani, Francesca ; Turner, Kevin ; Chiu, Ya Lin ; Wild, Peter J. ; Dolgalev, Igor ; Heguy, Adriana ; Sboner, Andrea ; Ramazangolu, Sinan ; Hieronymus, Haley ; Sawyers, Charles ; Tewari, Ashutosh K. ; Moch, Holger ; Yoon, Ghil Suk ; Known, Yong Chul ; Andrén, Ove ; Fall, Katja ; Demichelis, Francecsa ; Mosquera, Juan Miguel ; Robinson, Brian D. ; Barbieri, Christopher E. ; Rubin, Mark A. / SPOP mutations in prostate cancer across demographically diverse patient cohorts. In: Neoplasia (United States). 2014 ; Vol. 16, No. 1. pp. 14-20.
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title = "SPOP mutations in prostate cancer across demographically diverse patient cohorts",
abstract = "BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur in up to 15{\%} of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown. OBJECTIVE: To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material. DESIGN, SETTING, AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features. RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations was 8.1{\%} (4.6{\%} to 14.4{\%}), SPOP mutation was inversely associated with ERG rearrangement (P < .01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1 deletions (P < .01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes. CONCLUSION: SPOP is mutated in 4.6{\%} to 14.4{\%} of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.",
author = "Mirjam Blattner and Lee, {Daniel J.} and Catherine O'Reilly and Kyung Park and MacDonald, {Theresa Y.} and Francesca Khani and Kevin Turner and Chiu, {Ya Lin} and Wild, {Peter J.} and Igor Dolgalev and Adriana Heguy and Andrea Sboner and Sinan Ramazangolu and Haley Hieronymus and Charles Sawyers and Tewari, {Ashutosh K.} and Holger Moch and Yoon, {Ghil Suk} and Known, {Yong Chul} and Ove Andr{\'e}n and Katja Fall and Francecsa Demichelis and Mosquera, {Juan Miguel} and Robinson, {Brian D.} and Barbieri, {Christopher E.} and Rubin, {Mark A.}",
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T1 - SPOP mutations in prostate cancer across demographically diverse patient cohorts

AU - Blattner, Mirjam

AU - Lee, Daniel J.

AU - O'Reilly, Catherine

AU - Park, Kyung

AU - MacDonald, Theresa Y.

AU - Khani, Francesca

AU - Turner, Kevin

AU - Chiu, Ya Lin

AU - Wild, Peter J.

AU - Dolgalev, Igor

AU - Heguy, Adriana

AU - Sboner, Andrea

AU - Ramazangolu, Sinan

AU - Hieronymus, Haley

AU - Sawyers, Charles

AU - Tewari, Ashutosh K.

AU - Moch, Holger

AU - Yoon, Ghil Suk

AU - Known, Yong Chul

AU - Andrén, Ove

AU - Fall, Katja

AU - Demichelis, Francecsa

AU - Mosquera, Juan Miguel

AU - Robinson, Brian D.

AU - Barbieri, Christopher E.

AU - Rubin, Mark A.

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown. OBJECTIVE: To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material. DESIGN, SETTING, AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features. RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement (P < .01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1 deletions (P < .01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes. CONCLUSION: SPOP is mutated in 4.6% to 14.4% of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.

AB - BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown. OBJECTIVE: To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material. DESIGN, SETTING, AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features. RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement (P < .01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1 deletions (P < .01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes. CONCLUSION: SPOP is mutated in 4.6% to 14.4% of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.

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