SPOP and CHD1 alterations in prostate cancer: Relationship with PTEN loss, tumor grade, perineural infiltration, and PSA recurrence

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  • dc.contributor.author Hernández Llodrà, Silvia
  • dc.contributor.author Segalés Tañà, Laura, 1994-
  • dc.contributor.author Juanpere, Nuria
  • dc.contributor.author Lorenzo Perez, Marta
  • dc.contributor.author Salido Galeote, Marta
  • dc.contributor.author Nonell Mazelon, Lara, 1972-
  • dc.contributor.author López Martos, David
  • dc.contributor.author Rodríguez-Vida, Alejo
  • dc.contributor.author Bellmunt Molins, Joaquim, 1959-
  • dc.contributor.author Fumadó Ciutat, Lluis
  • dc.contributor.author Cecchini Rosell, Lluís
  • dc.contributor.author Lloreta, Josep, 1958-
  • dc.date.accessioned 2022-05-17T05:55:27Z
  • dc.date.available 2022-05-17T05:55:27Z
  • dc.date.issued 2021
  • dc.description.abstract Background: In the non-ETS fusion of prostate cancer (PCa) pathway, SPOP mutations emerge as a distinct oncogenic driver subclass. Both SPOP downregulation and mutation can lead to SPOP target stabilization promoting dysregulation of key regulatory pathways. CHD1 gene is commonly deleted in PCa. CHD1 loss significantly co-occurs with SPOP mutations, resulting in a PCa subclass with increased AR transcriptional activity and with a specific epigenetic pattern. Methods: In this study, SPOP alterations at mutational and protein levels and CHD1 copy number alterations have been analyzed and correlated with ERG and PTEN protein expression and with the clinical pathological features of the patients. Results: SPOP protein loss has been detected in 42.9% of the cases, and it has been strongly associated with PTEN protein loss (p < .001). CHD1 gene loss has been detected in 24.5% and SPOP mutations in 5.9% of the cases. Loss of CHD1 has been strongly associated with SPOP mutations (p = .003) and has shown a trend to be associated with ERG wt cancers (p = .08). The loss of SPOP protein (p = .01) and the combination of PTEN and SPOP protein loss (p = .002) were both statistically more common in grade group 5 cancers, with a prevalence of 60% and 37.5%, respectively. Furthermore, SPOP loss/PTEN loss and SPOP wt/PTEN loss phenotypes were strongly associated with extraprostatic perineural infiltration (p = .007). Strong CHD1 loss was associated with a shorter time to PSA recurrence in the univariate (p = .04), and showed a trend to be associated with the PSA recurrence risk in the multivariate analysis (p = .058). Conclusions: The results of the present study suggest that the loss of SPOP protein expression, either alone or in combination with loss of PTEN and, on the other hand, a marked loss of the CHD1 gene are very promising prognostic biomarkers in PCa.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Hernández-Llodrà S, Segalés L, Juanpere N, Marta Lorenzo T, Salido M, Nonell L, David López T, Rodríguez-Vida A, Bellmunt J, Fumadó L, Cecchini L, Lloreta-Trull J. SPOP and CHD1 alterations in prostate cancer: Relationship with PTEN loss, tumor grade, perineural infiltration, and PSA recurrence. Prostate. 2021 Dec;81(16):1267-77. DOI: 10.1002/pros.24218
  • dc.identifier.doi http://dx.doi.org/10.1002/pros.24218
  • dc.identifier.issn 0270-4137
  • dc.identifier.uri http://hdl.handle.net/10230/53100
  • dc.language.iso eng
  • dc.publisher Wiley
  • dc.relation.ispartof Prostate. 2021 Dec;81(16):1267-77
  • dc.rights © 2021 The Authors. The Prostate published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword CHD1
  • dc.subject.keyword PSA recurrence
  • dc.subject.keyword PTEN
  • dc.subject.keyword SPOP
  • dc.subject.keyword Prostate cancer
  • dc.title SPOP and CHD1 alterations in prostate cancer: Relationship with PTEN loss, tumor grade, perineural infiltration, and PSA recurrence
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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