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CASP8 SNP D302H (rs1045485) is associated with worse survival in MYCN-amplified neuroblastoma patients.

Rihani A, De Wilde B, Zeka F, Laureys G, Francotte N, Tonini GP, Coco S, Versteeg R, Noguera R, Schulte JH, Eggert A, Stallings RL, Speleman F, Vandesompele J, Van Maerken T - PLoS ONE (2014)

Bottom Line: Neuroblastoma is a pediatric cancer that exhibits a wide clinical spectrum ranging from spontaneous regression in low-risk patients to fatal disease in high-risk patients.SNPs in the TP53 pathway are of special importance, as several studies have reported associations between TP53 pathway SNPs and cancer.A missense SNP in exon 10 of the CASP8 gene SNP D302H was associated with worse overall and event-free survival in patients with MYCN-amplified neuroblastoma tumors.

View Article: PubMed Central - PubMed

Affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.

ABSTRACT

Background: Neuroblastoma is a pediatric cancer that exhibits a wide clinical spectrum ranging from spontaneous regression in low-risk patients to fatal disease in high-risk patients. The identification of single nucleotide polymorphisms (SNPs) may help explain the heterogeneity of neuroblastoma and assist in identifying patients at higher risk for poor survival. SNPs in the TP53 pathway are of special importance, as several studies have reported associations between TP53 pathway SNPs and cancer. Of note, less than 2% of neuroblastoma tumors have a TP53 mutation at diagnosis.

Patients and methods: We selected 21 of the most frequently studied SNPs in the TP53 pathway and evaluated their association with outcome in 500 neuroblastoma patients using TaqMan allelic discrimination assays.

Results and conclusion: We investigated the impact of 21 SNPs on overall survival, event-free survival, age at diagnosis, MYCN status, and stage of the disease in 500 neuroblastoma patients. A missense SNP in exon 10 of the CASP8 gene SNP D302H was associated with worse overall and event-free survival in patients with MYCN-amplified neuroblastoma tumors.

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Expression of caspase-8 by CASP8 SNP D302H.Comparison of caspase-8 expression between the different genotype groups of CASP8 SNP D302H. Cohort 1 (A), Cohort 2 (B). P-values were calculated by the Mann-Whitney U test. q-values are adjusted p-values after Benjamini-Hochberg multiple testing correction.
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pone-0114696-g002: Expression of caspase-8 by CASP8 SNP D302H.Comparison of caspase-8 expression between the different genotype groups of CASP8 SNP D302H. Cohort 1 (A), Cohort 2 (B). P-values were calculated by the Mann-Whitney U test. q-values are adjusted p-values after Benjamini-Hochberg multiple testing correction.

Mentions: Since decreased expression of caspase 8 is a recurrent event in NB [18], we tested whether CASP8 SNP D302H could affect the expression of caspase 8. We measured caspase 8 mRNA expression in two independent cohorts of NB tumor samples. Cohort 1 included 162 samples treated according to the International Society of Pediatric Oncology Europe Neuroblastoma Group (SIOPEN, https://www.siopen-r-net.org/). Cohort 2 included 161 samples from the Neuroblastoma Research Consortium (NRC), which is a collaboration between several European NB research groups. All samples from cohorts 1 and 2 were derived from patients that had been included in the entire cohort of 500 patients analyzed in Table 1. We found that CASP8 SNP D302H had no effect on caspase 8 mRNA expression levels, regardless of MYCN status or the stage of the disease (Table 4, Fig. 2).


CASP8 SNP D302H (rs1045485) is associated with worse survival in MYCN-amplified neuroblastoma patients.

Rihani A, De Wilde B, Zeka F, Laureys G, Francotte N, Tonini GP, Coco S, Versteeg R, Noguera R, Schulte JH, Eggert A, Stallings RL, Speleman F, Vandesompele J, Van Maerken T - PLoS ONE (2014)

Expression of caspase-8 by CASP8 SNP D302H.Comparison of caspase-8 expression between the different genotype groups of CASP8 SNP D302H. Cohort 1 (A), Cohort 2 (B). P-values were calculated by the Mann-Whitney U test. q-values are adjusted p-values after Benjamini-Hochberg multiple testing correction.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263607&req=5

pone-0114696-g002: Expression of caspase-8 by CASP8 SNP D302H.Comparison of caspase-8 expression between the different genotype groups of CASP8 SNP D302H. Cohort 1 (A), Cohort 2 (B). P-values were calculated by the Mann-Whitney U test. q-values are adjusted p-values after Benjamini-Hochberg multiple testing correction.
Mentions: Since decreased expression of caspase 8 is a recurrent event in NB [18], we tested whether CASP8 SNP D302H could affect the expression of caspase 8. We measured caspase 8 mRNA expression in two independent cohorts of NB tumor samples. Cohort 1 included 162 samples treated according to the International Society of Pediatric Oncology Europe Neuroblastoma Group (SIOPEN, https://www.siopen-r-net.org/). Cohort 2 included 161 samples from the Neuroblastoma Research Consortium (NRC), which is a collaboration between several European NB research groups. All samples from cohorts 1 and 2 were derived from patients that had been included in the entire cohort of 500 patients analyzed in Table 1. We found that CASP8 SNP D302H had no effect on caspase 8 mRNA expression levels, regardless of MYCN status or the stage of the disease (Table 4, Fig. 2).

Bottom Line: Neuroblastoma is a pediatric cancer that exhibits a wide clinical spectrum ranging from spontaneous regression in low-risk patients to fatal disease in high-risk patients.SNPs in the TP53 pathway are of special importance, as several studies have reported associations between TP53 pathway SNPs and cancer.A missense SNP in exon 10 of the CASP8 gene SNP D302H was associated with worse overall and event-free survival in patients with MYCN-amplified neuroblastoma tumors.

View Article: PubMed Central - PubMed

Affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.

ABSTRACT

Background: Neuroblastoma is a pediatric cancer that exhibits a wide clinical spectrum ranging from spontaneous regression in low-risk patients to fatal disease in high-risk patients. The identification of single nucleotide polymorphisms (SNPs) may help explain the heterogeneity of neuroblastoma and assist in identifying patients at higher risk for poor survival. SNPs in the TP53 pathway are of special importance, as several studies have reported associations between TP53 pathway SNPs and cancer. Of note, less than 2% of neuroblastoma tumors have a TP53 mutation at diagnosis.

Patients and methods: We selected 21 of the most frequently studied SNPs in the TP53 pathway and evaluated their association with outcome in 500 neuroblastoma patients using TaqMan allelic discrimination assays.

Results and conclusion: We investigated the impact of 21 SNPs on overall survival, event-free survival, age at diagnosis, MYCN status, and stage of the disease in 500 neuroblastoma patients. A missense SNP in exon 10 of the CASP8 gene SNP D302H was associated with worse overall and event-free survival in patients with MYCN-amplified neuroblastoma tumors.

Show MeSH
Related in: MedlinePlus