JNCI Journal of the National Cancer Institute, 2014
TP53 is the most frequently mutated gene in human malignancies; however, de novo somatic mutation... more TP53 is the most frequently mutated gene in human malignancies; however, de novo somatic mutations in childhood embryonal cancers such as neuroblastoma are rare. We report on the analysis of three independent case-control cohorts comprising 10 290 individuals and demonstrate that rs78378222 and rs35850753, rare germline variants in linkage disequilibrium that map to the 3´ untranslated region (UTR) of TP53 and 5´ UTR of the Δ133 isoform of TP53, respectively, are robustly associated with neuroblastoma (rs35850753: odds ratio [OR] = 2.7, 95% confidence interval [CI] = 2.0 to 3.6, P combined = 3.43 × 10 −12 ; rs78378222: OR = 2.3, 95% CI = 1.8 to 2.9, P combined = 2.03 × 10 −11 ). All statistical tests were two-sided. These findings add neuroblastoma to the complex repertoire of human cancers influenced by the rs78378222 hypomorphic allele, which impairs proper termination and polyadenylation of TP53 transcripts. Future studies using whole-genome sequencing data are likely to reveal additional rare variants with large effect sizes contributing to neuroblastoma tumorigenesis. * A1, allele, on forward strand; A2: allele 2, on forward strand; CI, confidence interval; OR, odds ratio with respect to A1; SNP, single nucleotide polymorophism. † No deviations from Hardy-Weinberg equilibrium were observed (P > .001) in all cohorts. ‡ Allelic P values generated by SNPTEST score method (two-sided); combined P values from METAL using inverse-variance method (two-sided).
DESIGN: Retrospective cohort study. MATERIALS AND METHODS: We stratified our sample into 3 groups... more DESIGN: Retrospective cohort study. MATERIALS AND METHODS: We stratified our sample into 3 groups: Those with an SMR in the prior year, those with a polypectomy, and those with no surgery. Groups were matched by age, parity, protocol, # of prior IVF cycles and mature oocytes. One-way ANOVA and Chi-square tests were used. We compared outcome between those who did IVF within 3 months of surgery and those who waited longer. Student's t-test was used.
JNCI Journal of the National Cancer Institute, 2014
TP53 is the most frequently mutated gene in human malignancies; however, de novo somatic mutation... more TP53 is the most frequently mutated gene in human malignancies; however, de novo somatic mutations in childhood embryonal cancers such as neuroblastoma are rare. We report on the analysis of three independent case-control cohorts comprising 10 290 individuals and demonstrate that rs78378222 and rs35850753, rare germline variants in linkage disequilibrium that map to the 3´ untranslated region (UTR) of TP53 and 5´ UTR of the Δ133 isoform of TP53, respectively, are robustly associated with neuroblastoma (rs35850753: odds ratio [OR] = 2.7, 95% confidence interval [CI] = 2.0 to 3.6, P combined = 3.43 × 10 −12 ; rs78378222: OR = 2.3, 95% CI = 1.8 to 2.9, P combined = 2.03 × 10 −11 ). All statistical tests were two-sided. These findings add neuroblastoma to the complex repertoire of human cancers influenced by the rs78378222 hypomorphic allele, which impairs proper termination and polyadenylation of TP53 transcripts. Future studies using whole-genome sequencing data are likely to reveal additional rare variants with large effect sizes contributing to neuroblastoma tumorigenesis. * A1, allele, on forward strand; A2: allele 2, on forward strand; CI, confidence interval; OR, odds ratio with respect to A1; SNP, single nucleotide polymorophism. † No deviations from Hardy-Weinberg equilibrium were observed (P > .001) in all cohorts. ‡ Allelic P values generated by SNPTEST score method (two-sided); combined P values from METAL using inverse-variance method (two-sided).
DESIGN: Retrospective cohort study. MATERIALS AND METHODS: We stratified our sample into 3 groups... more DESIGN: Retrospective cohort study. MATERIALS AND METHODS: We stratified our sample into 3 groups: Those with an SMR in the prior year, those with a polypectomy, and those with no surgery. Groups were matched by age, parity, protocol, # of prior IVF cycles and mature oocytes. One-way ANOVA and Chi-square tests were used. We compared outcome between those who did IVF within 3 months of surgery and those who waited longer. Student's t-test was used.
Uploads
Papers by M. Diamond