FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4324136431> ?p ?o ?g. }

• W4324136431 endingPage "202" @default.
• W4324136431 startingPage "202" @default.
• W4324136431 abstract "202 Background: Speckle-type POZ protein (SPOP) mutations are a frequent initiating event in prostate cancer (PC) and are associated with increased androgen receptor transcriptional output. While SPOP-Mutant (MT) PCs may be more sensitive to hormonal therapy, they are still common amongst castration-resistant PCs (CRPCs) and frequently lethal. It remains unknown which SPOP MT PCs will respond well to hormonal therapy, and which have the potential to develop early castration resistance and cause patient death. Methods: With IRB approval, we retrospectively analyzed NGS data obtained via Tempus|xT tissue assay (DNA sequencing of 648 genes in tumor and matched normal samples at 500x depth) and/or Tempus|xF liquid biopsy assay (ctDNA sequencing of 105 genes in peripheral blood samples at 5,000x depth) for germline and/or somatic mutations in 234 consecutive patients with high-risk localized, locally advanced or metastatic PC followed at Ben Taub Hospital (BTH), a public hospital serving a racially/ethnically diverse patient population (>50% of PC patients are African American). For confirmation, we examined de-identified NGS data from a nationwide cohort of 8812 PC patients sequenced with xT and/or xF by Tempus Labs (Chicago, IL), as well as publicly available data from four additional PC cohorts (PMIDs: 26544944, 34667026, 31061129 and 26855148). Results: We found SPOP mutations in 31/234 BTH PC patients (13.2%). Eleven of these 31 patients (35.5%) also exhibited loss-of-function (LOF) mutations or deletions in the tumor suppressor gene Adenomatous polyposis coli (APC). APC LOF events were found only in 15/203 (7.4%) of the SPOP-wild type (WT) PCs, and the enrichment of SPOP MT PCs for APC LOF events was highly significant (Chi square with Yates correction: P<0.00001). The co-mutation pattern between these two genes was observed even when the analysis was limited specifically to the tissue NGS (133 patients) or the liquid biopsy NGS subsets of the dataset, respectively. This enrichment was confirmed in the nationwide TEMPUS cohort and in the four publicly available clinical PC datasets (APC LOF found in 23.4, 27.0, 21.5, 32.0 and 30.8% of SPOP MT PCs, respectively; and only in 5.8, 2.4, 6.0, 6.7 and 1.0% of SPOP-Wild Type (WT) PCs, respectively (P<0.001 in each cohort). In the BTH PC cohort, SPOP MT PCs harboring APC LOF mutations were more likely to present with metastatic disease (M1) at diagnosis and to develop castration-resistance within 1 year of first-line hormonal therapy than SPOP MT PCs with WT APC. Conclusions: In SPOP MT PCs, inactivation of APC is a common event and associated with more aggressive disease (higher metastatic potential and faster progression to castration resistance). This observation may help identify SPOP MT PC patients who are at higher risk for early castration resistance and could benefit from more intensive treatment." @default.
• W4324136431 created "2023-03-15" @default.
• W4324136431 creator A5003577583 @default.
• W4324136431 creator A5006630838 @default.
• W4324136431 creator A5008386087 @default.
• W4324136431 creator A5014866366 @default.
• W4324136431 creator A5018430323 @default.
• W4324136431 creator A5026480927 @default.
• W4324136431 creator A5039206976 @default.
• W4324136431 creator A5044181467 @default.
• W4324136431 creator A5059536578 @default.
• W4324136431 creator A5063176180 @default.
• W4324136431 creator A5073398031 @default.
• W4324136431 date "2023-02-20" @default.
• W4324136431 modified "2023-09-25" @default.
• W4324136431 title "Role of adenomatous polyposis coli (APC) gene in SPOP-mutant prostate cancer and clinical outcomes." @default.
• W4324136431 doi "https://doi.org/10.1200/jco.2023.41.6_suppl.202" @default.
• W4324136431 hasPublicationYear "2023" @default.
• W4324136431 type Work @default.
• W4324136431 citedByCount "0" @default.
• W4324136431 crossrefType "journal-article" @default.
• W4324136431 hasAuthorship W4324136431A5003577583 @default.
• W4324136431 hasAuthorship W4324136431A5006630838 @default.
• W4324136431 hasAuthorship W4324136431A5008386087 @default.
• W4324136431 hasAuthorship W4324136431A5014866366 @default.
• W4324136431 hasAuthorship W4324136431A5018430323 @default.
• W4324136431 hasAuthorship W4324136431A5026480927 @default.
• W4324136431 hasAuthorship W4324136431A5039206976 @default.
• W4324136431 hasAuthorship W4324136431A5044181467 @default.
• W4324136431 hasAuthorship W4324136431A5059536578 @default.
• W4324136431 hasAuthorship W4324136431A5063176180 @default.
• W4324136431 hasAuthorship W4324136431A5073398031 @default.
• W4324136431 hasConcept C104317684 @default.
• W4324136431 hasConcept C109825262 @default.
• W4324136431 hasConcept C121608353 @default.
• W4324136431 hasConcept C126322002 @default.
• W4324136431 hasConcept C143998085 @default.
• W4324136431 hasConcept C2778237340 @default.
• W4324136431 hasConcept C2780192828 @default.
• W4324136431 hasConcept C2781187634 @default.
• W4324136431 hasConcept C2908647359 @default.
• W4324136431 hasConcept C502942594 @default.
• W4324136431 hasConcept C526805850 @default.
• W4324136431 hasConcept C54355233 @default.
• W4324136431 hasConcept C71924100 @default.
• W4324136431 hasConcept C86803240 @default.
• W4324136431 hasConcept C99454951 @default.
• W4324136431 hasConceptScore W4324136431C104317684 @default.
• W4324136431 hasConceptScore W4324136431C109825262 @default.
• W4324136431 hasConceptScore W4324136431C121608353 @default.
• W4324136431 hasConceptScore W4324136431C126322002 @default.
• W4324136431 hasConceptScore W4324136431C143998085 @default.
• W4324136431 hasConceptScore W4324136431C2778237340 @default.
• W4324136431 hasConceptScore W4324136431C2780192828 @default.
• W4324136431 hasConceptScore W4324136431C2781187634 @default.
• W4324136431 hasConceptScore W4324136431C2908647359 @default.
• W4324136431 hasConceptScore W4324136431C502942594 @default.
• W4324136431 hasConceptScore W4324136431C526805850 @default.
• W4324136431 hasConceptScore W4324136431C54355233 @default.
• W4324136431 hasConceptScore W4324136431C71924100 @default.
• W4324136431 hasConceptScore W4324136431C86803240 @default.
• W4324136431 hasConceptScore W4324136431C99454951 @default.
• W4324136431 hasIssue "6_suppl" @default.
• W4324136431 hasLocation W43241364311 @default.
• W4324136431 hasOpenAccess W4324136431 @default.
• W4324136431 hasPrimaryLocation W43241364311 @default.
• W4324136431 hasRelatedWork W2019279330 @default.
• W4324136431 hasRelatedWork W2038603726 @default.
• W4324136431 hasRelatedWork W2049754458 @default.
• W4324136431 hasRelatedWork W2313360580 @default.
• W4324136431 hasRelatedWork W2350493697 @default.
• W4324136431 hasRelatedWork W2972637542 @default.
• W4324136431 hasRelatedWork W2972884351 @default.
• W4324136431 hasRelatedWork W3026015583 @default.
• W4324136431 hasRelatedWork W3180628252 @default.
• W4324136431 hasRelatedWork W2588285805 @default.
• W4324136431 hasVolume "41" @default.
• W4324136431 isParatext "false" @default.
• W4324136431 isRetracted "false" @default.
• W4324136431 workType "article" @default.