Contribution of ARLTS1 Cys148Arg (T442C) variant with prostate cancer risk and ARLTS1 function in prostate cancer cells.

ARLTS1 is a recently characterized tumor suppressor gene at 13q14.3, a region frequently deleted in both sporadic and hereditary prostate cancer (PCa). ARLTS1 variants, especially Cys148Arg (T442C), increase susceptibility to different cancers, including PCa. In this study the role of Cys148Arg subs...

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Autores principales:	Sanna Siltanen, Tiina Wahlfors, Martin Schindler, Outi R Saramäki, John Patrick Mpindi, Leena Latonen, Robert L Vessella, Teuvo L J Tammela, Olli Kallioniemi, Tapio Visakorpi, Johanna Schleutker
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1590925213ea4b3aa63622c9307f2430
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spelling	oai:doaj.org-article:1590925213ea4b3aa63622c9307f24302021-11-18T07:36:00ZContribution of ARLTS1 Cys148Arg (T442C) variant with prostate cancer risk and ARLTS1 function in prostate cancer cells.1932-620310.1371/journal.pone.0026595https://doaj.org/article/1590925213ea4b3aa63622c9307f24302011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22028916/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203ARLTS1 is a recently characterized tumor suppressor gene at 13q14.3, a region frequently deleted in both sporadic and hereditary prostate cancer (PCa). ARLTS1 variants, especially Cys148Arg (T442C), increase susceptibility to different cancers, including PCa. In this study the role of Cys148Arg substitution was investigated as a risk factor for PCa using both genetic and functional analysis. Cys148Arg genotypes and expression of the ARLTS1 were explored in a large set of familial and unselected PCa cases, clinical tumor samples, xenografts, prostate cancer cell lines and benign prostatic hyperplasia (BPH) samples. The frequency of the variant genotype CC was significantly higher in familial (OR = 1.67, 95% CI = 1.08-2.56, P = 0.019) and unselected patients (OR = 1.52, 95% CI = 1.18-1.97, P = 0.001) and the overall risk was increased (OR = 1.54, 95% CI = 1.20-1.98, P = 0.0007). Additional analysis with clinicopathological data revealed an association with an aggressive disease (OR = 1.28, 95% CI = 1.05-∞, P = 0.02). The CC genotype of the Cys148Arg variant was also contributing to the lowered ARLTS1 expression status in lymphoblastoid cells from familial patients. In addition significantly lowered ARLTS1 expression was observed in clinical tumor samples compared to BPH samples (P = 0.01). The ARLTS1 co-expression signature based on previously published microarray data was generated from 1587 cancer samples confirming the low expression of ARLTS1 in PCa and showed that ARLTS1 expression was strongly associated with immune processes. This study provides strong confirmation of the important role of ARLTS1 Cys148Arg variant as a contributor in PCa predisposition and a potential marker for aggressive disease outcome.Sanna SiltanenTiina WahlforsMartin SchindlerOuti R SaramäkiJohn Patrick MpindiLeena LatonenRobert L VessellaTeuvo L J TammelaOlli KallioniemiTapio VisakorpiJohanna SchleutkerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e26595 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sanna Siltanen Tiina Wahlfors Martin Schindler Outi R Saramäki John Patrick Mpindi Leena Latonen Robert L Vessella Teuvo L J Tammela Olli Kallioniemi Tapio Visakorpi Johanna Schleutker Contribution of ARLTS1 Cys148Arg (T442C) variant with prostate cancer risk and ARLTS1 function in prostate cancer cells.
description	ARLTS1 is a recently characterized tumor suppressor gene at 13q14.3, a region frequently deleted in both sporadic and hereditary prostate cancer (PCa). ARLTS1 variants, especially Cys148Arg (T442C), increase susceptibility to different cancers, including PCa. In this study the role of Cys148Arg substitution was investigated as a risk factor for PCa using both genetic and functional analysis. Cys148Arg genotypes and expression of the ARLTS1 were explored in a large set of familial and unselected PCa cases, clinical tumor samples, xenografts, prostate cancer cell lines and benign prostatic hyperplasia (BPH) samples. The frequency of the variant genotype CC was significantly higher in familial (OR = 1.67, 95% CI = 1.08-2.56, P = 0.019) and unselected patients (OR = 1.52, 95% CI = 1.18-1.97, P = 0.001) and the overall risk was increased (OR = 1.54, 95% CI = 1.20-1.98, P = 0.0007). Additional analysis with clinicopathological data revealed an association with an aggressive disease (OR = 1.28, 95% CI = 1.05-∞, P = 0.02). The CC genotype of the Cys148Arg variant was also contributing to the lowered ARLTS1 expression status in lymphoblastoid cells from familial patients. In addition significantly lowered ARLTS1 expression was observed in clinical tumor samples compared to BPH samples (P = 0.01). The ARLTS1 co-expression signature based on previously published microarray data was generated from 1587 cancer samples confirming the low expression of ARLTS1 in PCa and showed that ARLTS1 expression was strongly associated with immune processes. This study provides strong confirmation of the important role of ARLTS1 Cys148Arg variant as a contributor in PCa predisposition and a potential marker for aggressive disease outcome.
format	article
author	Sanna Siltanen Tiina Wahlfors Martin Schindler Outi R Saramäki John Patrick Mpindi Leena Latonen Robert L Vessella Teuvo L J Tammela Olli Kallioniemi Tapio Visakorpi Johanna Schleutker
author_facet	Sanna Siltanen Tiina Wahlfors Martin Schindler Outi R Saramäki John Patrick Mpindi Leena Latonen Robert L Vessella Teuvo L J Tammela Olli Kallioniemi Tapio Visakorpi Johanna Schleutker
author_sort	Sanna Siltanen
title	Contribution of ARLTS1 Cys148Arg (T442C) variant with prostate cancer risk and ARLTS1 function in prostate cancer cells.
title_short	Contribution of ARLTS1 Cys148Arg (T442C) variant with prostate cancer risk and ARLTS1 function in prostate cancer cells.
title_full	Contribution of ARLTS1 Cys148Arg (T442C) variant with prostate cancer risk and ARLTS1 function in prostate cancer cells.
title_fullStr	Contribution of ARLTS1 Cys148Arg (T442C) variant with prostate cancer risk and ARLTS1 function in prostate cancer cells.
title_full_unstemmed	Contribution of ARLTS1 Cys148Arg (T442C) variant with prostate cancer risk and ARLTS1 function in prostate cancer cells.
title_sort	contribution of arlts1 cys148arg (t442c) variant with prostate cancer risk and arlts1 function in prostate cancer cells.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/1590925213ea4b3aa63622c9307f2430
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Contribution of ARLTS1 Cys148Arg (T442C) variant with prostate cancer risk and ARLTS1 function in prostate cancer cells.

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