The 5'UTR variant of ERCC5 fails to influence outcomes in ovarian and lung cancer patients undergoing treatment with platinum-based drugs.

Eliana Rulli,Federica Guffanti,Lorenzo Ceppi,Elisa Caiola,Monica Ganzinelli,Sheila Piva,Marina C Garassino,Giovanna Damia,Mirko Marabese,Massimo Broggini

doi:10.1038/srep39217

Abstract

The common polymorphic variant in the 5′ untranslated region of the excision repair cross-complementation group 5 (ERCC5) gene was described to generate an upstream open reading frame that regulates both the basal ERCC5 expression and its ability to be synthesized following DNA damage. This variant was reported to affect response to platinum therapy in a cohort of patients with pediatric ependymoma. The role of this variant was investigated in two cohorts of cancer patients, specifically in non-small-cell lung cancer (NSCLC) patients (N = 137) and in epithelial ovarian carcinoma (EOC) patients (N = 240), treated in first-line with platinum-based compounds. Differently from what reported for pediatric ependymoma, the analysis of the polymorphism in NSCLC patients cohort was not able to detect any difference among patients harboring different genotypes both in progression free survival (HR = 0.93; 95%CI 0.64–1.33; p-value = 0.678) and overall survival (HR = 0.90; 95%CI 0.62–1.33; p-value = 0.625). These data were corroborated in a EOC patients cohort, where similar progression free survival (HR = 0.91; 95% CI 0.67–1.24; p-value = 0.561) and overall survival (HR = 0.98; 95% CI 0.71–1.35; p-value = 0.912) were found for the different genotypes. These data, obtained in appropriately sized populations, indicate that the effect of this ERCC5 polymorphism is likely to be relevant only in specific tumors.

Highlights

The common polymorphic variant in the 5′ untranslated region of the excision repair crosscomplementation group 5 (ERCC5) gene was described to generate an upstream open reading frame that regulates both the basal Excision repair cross-complementation group 5 (ERCC5) expression and its ability to be synthesized following DNA damage
Excision repair cross-complementation group 5 (ERCC5), known as Xeroderma pigmentosum group G (XPG), is a gene belonging to nucleotide excision repair (NER) that encodes a single-strand specific endonuclease that makes the 3′incision in the DNA repair process following damage
It is well known that some somatic mutations or rearrangements such as gene duplication or deletion in the tumor define subgroup of patients more responsive to chemotherapy[11,12]

Summary

Introduction

The common polymorphic variant in the 5′ untranslated region of the excision repair crosscomplementation group 5 (ERCC5) gene was described to generate an upstream open reading frame that regulates both the basal ERCC5 expression and its ability to be synthesized following DNA damage This variant was reported to affect response to platinum therapy in a cohort of patients with pediatric ependymoma. The common polymorphic variant in the ERCC5 5′untranslated region (rs751402) was described to generate an upstream Open Reading Frame (uORF) that affects both the basal ERCC5 expression and its ability to be synthesized following DNA damage This variant was reported to affect the response to platinum therapy in a cohort www.nature.com/scientificreports/

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Conclusion