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Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed

BACKGROUND: We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed. METHODS: Twenty-five patients treated with pemetrexed-based regimens were included....

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Autores principales: Arévalo, Estefanía, Castañón, Eduardo, López, Inés, Salgado, Josefa, Collado, Víctor, Santisteban, Marta, Rodríguez-Ruiz, María, Martín, Patricia, Zubiri, Leire, Patiño-García, Ana, Rolfo, Christian, Gil-Bazo, Ignacio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996904/
https://www.ncbi.nlm.nih.gov/pubmed/24726028
http://dx.doi.org/10.1186/1479-5876-12-98
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author Arévalo, Estefanía
Castañón, Eduardo
López, Inés
Salgado, Josefa
Collado, Víctor
Santisteban, Marta
Rodríguez-Ruiz, María
Martín, Patricia
Zubiri, Leire
Patiño-García, Ana
Rolfo, Christian
Gil-Bazo, Ignacio
author_facet Arévalo, Estefanía
Castañón, Eduardo
López, Inés
Salgado, Josefa
Collado, Víctor
Santisteban, Marta
Rodríguez-Ruiz, María
Martín, Patricia
Zubiri, Leire
Patiño-García, Ana
Rolfo, Christian
Gil-Bazo, Ignacio
author_sort Arévalo, Estefanía
collection PubMed
description BACKGROUND: We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed. METHODS: Twenty-five patients treated with pemetrexed-based regimens were included. Genomic DNA was isolated prior to treatment. The variable number of tandem repeat (VNTR) polymorphisms, the G > C single nucleotide polymorphisms (SNP) and the TS 6-bp insertion/deletion (6/6) in the 3′ untranslated region (UTR) polymorphisms were analyzed and correlated with overall response rate (ORR), progression-free survival (PFS), overall-survival (OS) and toxicity. RESULTS: The genotype +6/+6 predicted a higher ORR among active/former smokers compared to +6/-6 genotype (100% vs. 50%; p = 0.085). Overall, the 3R/3R genotype predicted a higher ORR (100%) over the rest VNTR polymorphisms (p = 0.055). The presence of 3R/3R genotype significantly correlated with a superior ORR in patients without EGFR activating mutations (100%) compared to 2R/2R, 2R/3R and 3R/4R genotype (77.8%, 33.3% and 0% respectively; p = 0.017). After a median follow-up of 21 months, a trend towards a better PFS, although not significant, was found among subjects showing 3R/3R polymorphisms (p = 0.089). A significantly superior OS was found in patients showing 3R/3R genotype rather than other VNTR polymorphisms (p = 0.019). No significant correlation with the toxicity was observed. CONCLUSION: In our series, 3R/3R polymorphism correlated with a superior OS. Also, this polymorphism, when associated to wild type EGFR, was related to a higher ORR to pemetrexed. Toxicity was not significantly correlated with a specific TS genotype.
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spelling pubmed-39969042014-04-24 Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed Arévalo, Estefanía Castañón, Eduardo López, Inés Salgado, Josefa Collado, Víctor Santisteban, Marta Rodríguez-Ruiz, María Martín, Patricia Zubiri, Leire Patiño-García, Ana Rolfo, Christian Gil-Bazo, Ignacio J Transl Med Research BACKGROUND: We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed. METHODS: Twenty-five patients treated with pemetrexed-based regimens were included. Genomic DNA was isolated prior to treatment. The variable number of tandem repeat (VNTR) polymorphisms, the G > C single nucleotide polymorphisms (SNP) and the TS 6-bp insertion/deletion (6/6) in the 3′ untranslated region (UTR) polymorphisms were analyzed and correlated with overall response rate (ORR), progression-free survival (PFS), overall-survival (OS) and toxicity. RESULTS: The genotype +6/+6 predicted a higher ORR among active/former smokers compared to +6/-6 genotype (100% vs. 50%; p = 0.085). Overall, the 3R/3R genotype predicted a higher ORR (100%) over the rest VNTR polymorphisms (p = 0.055). The presence of 3R/3R genotype significantly correlated with a superior ORR in patients without EGFR activating mutations (100%) compared to 2R/2R, 2R/3R and 3R/4R genotype (77.8%, 33.3% and 0% respectively; p = 0.017). After a median follow-up of 21 months, a trend towards a better PFS, although not significant, was found among subjects showing 3R/3R polymorphisms (p = 0.089). A significantly superior OS was found in patients showing 3R/3R genotype rather than other VNTR polymorphisms (p = 0.019). No significant correlation with the toxicity was observed. CONCLUSION: In our series, 3R/3R polymorphism correlated with a superior OS. Also, this polymorphism, when associated to wild type EGFR, was related to a higher ORR to pemetrexed. Toxicity was not significantly correlated with a specific TS genotype. BioMed Central 2014-04-14 /pmc/articles/PMC3996904/ /pubmed/24726028 http://dx.doi.org/10.1186/1479-5876-12-98 Text en Copyright © 2014 Arévalo et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Arévalo, Estefanía
Castañón, Eduardo
López, Inés
Salgado, Josefa
Collado, Víctor
Santisteban, Marta
Rodríguez-Ruiz, María
Martín, Patricia
Zubiri, Leire
Patiño-García, Ana
Rolfo, Christian
Gil-Bazo, Ignacio
Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed
title Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed
title_full Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed
title_fullStr Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed
title_full_unstemmed Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed
title_short Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed
title_sort thymidylate synthase polymorphisms in genomic dna as clinical outcome predictors in a european population of advanced non-small cell lung cancer patients receiving pemetrexed
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996904/
https://www.ncbi.nlm.nih.gov/pubmed/24726028
http://dx.doi.org/10.1186/1479-5876-12-98
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