Deep sequencing of the gene reveals a potential risk allele for non–small cell lung cancer and supports the negative prognostic value of variants
The TP53 gene remains the most frequently altered gene in human cancer, of which variants are associated with cancer risk, therapy resistance, and poor prognosis in several tumor types. To determine the true prognostic value of TP53 variants in non–small cell lung cancer, this study conducted furthe...
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doaj-d267590449764e62a32b505b79a0c4c12021-05-02T18:17:10ZengIOS PressTumor Biology1423-03802017-02-013910.1177/1010428317694327Deep sequencing of the gene reveals a potential risk allele for non–small cell lung cancer and supports the negative prognostic value of variantsChristophe Deben0Jolien Van den Bossche1Nele Van Der Steen2Filip Lardon3An Wouters4Ken Op de Beeck5Christophe Hermans6Julie Jacobs7Marc Peeters8Guy Van Camp9Christian Rolfo10Vanessa Deschoolmeester11Patrick Pauwels12Department of Pathology, Antwerp University Hospital, Antwerp, BelgiumCenter for Oncological Research (CORE), University of Antwerp, Antwerp, BelgiumDepartment of Pathology, Antwerp University Hospital, Antwerp, BelgiumCenter for Oncological Research (CORE), University of Antwerp, Antwerp, BelgiumCenter for Oncological Research (CORE), University of Antwerp, Antwerp, BelgiumCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, BelgiumDepartment of Pathology, Antwerp University Hospital, Antwerp, BelgiumDepartment of Pathology, Antwerp University Hospital, Antwerp, BelgiumDepartment of Medical Oncology, Antwerp University Hospital, Antwerp, BelgiumCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, BelgiumPhase-1 Early Clinical Trials Unit, Antwerp University Hospital, Antwerp, BelgiumDepartment of Pathology, Antwerp University Hospital, Antwerp, BelgiumDepartment of Pathology, Antwerp University Hospital, Antwerp, BelgiumThe TP53 gene remains the most frequently altered gene in human cancer, of which variants are associated with cancer risk, therapy resistance, and poor prognosis in several tumor types. To determine the true prognostic value of TP53 variants in non–small cell lung cancer, this study conducted further research, particularly focusing on subtype and tumor stage. Therefore, we determined the TP53 status of 97 non–small cell lung cancer adenocarcinoma patients using next generation deep sequencing technology and defined the prognostic value of frequently occurring single nucleotide polymorphisms and mutations in the TP53 gene. Inactivating TP53 mutations acted as a predictor for both worse overall and progression-free survival in stage II–IV patients and patients treated with DNA-damaging (neo)adjuvant therapy. In stage I tumors, the Pro-allele of the TP53 R72P polymorphism acted as a predictor for worse overall survival. In addition, we detected the rare R213R (rs1800372, minor allele frequency: 0.0054) polymorphism in 7.2% of the patients and are the first to show the significant association with TP53 mutations in non–small cell lung cancer adenocarcinoma patients (p = 0.003). In conclusion, Our findings show an important role for TP53 variants as negative predictors for the outcome of non–small cell lung cancer adenocarcinoma patients, especially for TP53 inactivating mutations in advanced stage tumors treated with DNA-damaging agents, and provide the first evidence of the R213R G-allele as possible risk factor for non–small cell lung cancer.https://doi.org/10.1177/1010428317694327 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christophe Deben Jolien Van den Bossche Nele Van Der Steen Filip Lardon An Wouters Ken Op de Beeck Christophe Hermans Julie Jacobs Marc Peeters Guy Van Camp Christian Rolfo Vanessa Deschoolmeester Patrick Pauwels |
spellingShingle |
Christophe Deben Jolien Van den Bossche Nele Van Der Steen Filip Lardon An Wouters Ken Op de Beeck Christophe Hermans Julie Jacobs Marc Peeters Guy Van Camp Christian Rolfo Vanessa Deschoolmeester Patrick Pauwels Deep sequencing of the gene reveals a potential risk allele for non–small cell lung cancer and supports the negative prognostic value of variants Tumor Biology |
author_facet |
Christophe Deben Jolien Van den Bossche Nele Van Der Steen Filip Lardon An Wouters Ken Op de Beeck Christophe Hermans Julie Jacobs Marc Peeters Guy Van Camp Christian Rolfo Vanessa Deschoolmeester Patrick Pauwels |
author_sort |
Christophe Deben |
title |
Deep sequencing of the gene reveals a potential risk allele for non–small cell lung cancer and supports the negative prognostic value of variants |
title_short |
Deep sequencing of the gene reveals a potential risk allele for non–small cell lung cancer and supports the negative prognostic value of variants |
title_full |
Deep sequencing of the gene reveals a potential risk allele for non–small cell lung cancer and supports the negative prognostic value of variants |
title_fullStr |
Deep sequencing of the gene reveals a potential risk allele for non–small cell lung cancer and supports the negative prognostic value of variants |
title_full_unstemmed |
Deep sequencing of the gene reveals a potential risk allele for non–small cell lung cancer and supports the negative prognostic value of variants |
title_sort |
deep sequencing of the gene reveals a potential risk allele for non–small cell lung cancer and supports the negative prognostic value of variants |
publisher |
IOS Press |
series |
Tumor Biology |
issn |
1423-0380 |
publishDate |
2017-02-01 |
description |
The TP53 gene remains the most frequently altered gene in human cancer, of which variants are associated with cancer risk, therapy resistance, and poor prognosis in several tumor types. To determine the true prognostic value of TP53 variants in non–small cell lung cancer, this study conducted further research, particularly focusing on subtype and tumor stage. Therefore, we determined the TP53 status of 97 non–small cell lung cancer adenocarcinoma patients using next generation deep sequencing technology and defined the prognostic value of frequently occurring single nucleotide polymorphisms and mutations in the TP53 gene. Inactivating TP53 mutations acted as a predictor for both worse overall and progression-free survival in stage II–IV patients and patients treated with DNA-damaging (neo)adjuvant therapy. In stage I tumors, the Pro-allele of the TP53 R72P polymorphism acted as a predictor for worse overall survival. In addition, we detected the rare R213R (rs1800372, minor allele frequency: 0.0054) polymorphism in 7.2% of the patients and are the first to show the significant association with TP53 mutations in non–small cell lung cancer adenocarcinoma patients (p = 0.003). In conclusion, Our findings show an important role for TP53 variants as negative predictors for the outcome of non–small cell lung cancer adenocarcinoma patients, especially for TP53 inactivating mutations in advanced stage tumors treated with DNA-damaging agents, and provide the first evidence of the R213R G-allele as possible risk factor for non–small cell lung cancer. |
url |
https://doi.org/10.1177/1010428317694327 |
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