{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pinto EM"],"funding":["American Lebanese Syrian Associated Charities - ALSAC","Rosetrees","NCI NIH HHS","Wellcome Trust"],"pagination":["eaba3231"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7314530"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(26)"],"pubmed_abstract":["Cancer risk is highly variable in carriers of the common <i>TP53-</i>R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor <i>XAF1</i> (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype was enriched in patients with cancer, conferring risk for sarcoma (<i>P</i> = 0.003) and subsequent malignancies (<i>P</i> = 0.006). Functional analyses demonstrated that wild-type XAF1 enhances transactivation of wild-type and hypomorphic <i>TP53</i> variants, whereas <i>XAF1</i>-E134* is markedly attenuated in this activity. We propose that cosegregation of <i>XAF1-</i>E134* a"],"journal":["Science advances"],"pubmed_title":["XAF1 as a modifier of p53 function and cancer susceptibility."],"pmcid":["PMC7314530"],"funding_grant_id":["P30 CA021765","100719/Z/12/Z","R01 CA217657","M505"],"pubmed_authors":["Vaur D","Connelly JP","Zhang J","Achatz MI","Pappo A","Wu G","Parise IZS","Wang J","Rampersaud E","Odone-Filho V","Machado M","Pinto EM","Yeager M","Ramos CRN","Chen W","Nichols KE","Lavarino C","Bittar CM","Fuster-Soler JL","Maxwell KN","Brugieres L","Hamilton KV","Korbonits M","Vogt A","Else T","Komechen H","Rodriguez-Galindo C","Mathias C","Costa TEB","Kowalski L","Jones K","Ashton-Prolla P","Figueiredo BC","Letouze E","Clay MR","Ribeiro RC","Neale G","Pruett-Miller S","Murphy AJ","Volc S","Stoffel EM","Soares EWS","Palmero EI","Ribeiro EMSF","Formiga MN","Galvao HCR","Almeida MQ","Fragoso MCBV","Savage SA","Paraizo MM","Thomas MG","Mendonca BB","Lalli E","Zambetti GP","de Andrade KC","Zhou W","Klincha PP","Brondani VB","Salvador H","Felix G","Santiago KM","Latronico AC","Diekmann Y","Chantada G"],"additional_accession":[]},"is_claimable":false,"name":"XAF1 as a modifier of p53 function and cancer susceptibility.","description":"Cancer risk is highly variable in carriers of the common <i>TP53-</i>R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor <i>XAF1</i> (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype was enriched in patients with cancer, conferring risk for sarcoma (<i>P</i> = 0.003) and subsequent malignancies (<i>P</i> = 0.006). Functional analyses demonstrated that wild-type XAF1 enhances transactivation of wild-type and hypomorphic <i>TP53</i> variants, whereas <i>XAF1</i>-E134* is markedly attenuated in this activity. We propose that cosegregation of <i>XAF1-</i>E134* a","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jun","modification":"2026-05-04T01:00:09.302Z","creation":"2020-07-10T07:16:42Z"},"accession":"S-EPMC7314530","cross_references":{"pubmed":["32637605"],"doi":["10.1126/sciadv.aba3231"]}}