FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3011105220> ?p ?o ?g. }

• W3011105220 abstract "Variants of unknown significance (VUS) occur in approximately 10% of BRCA1 and BRCA2 genetic testing. Definition of VUS as pathogenic or of benign potential is a crucial step in the reporting and counseling process. Thus limiting the clinical utility of a genetic test and impairs the correct patient management. BRCA1 and 2 are tumor suppressor genes and loss of heterozygosity (LoH) as a second hit for inactivating wildtype allele is a relatively common event in tumor. Previously, in a multi-institutional effort, AC Camargo Cancer Center (Brazil), Barretos Cancer Hospital (Brazil) and UTMD Anderson Cancer Center (USA) compiled a total of 332 BRCA1/2 VUS supposedly from unrelated carriers (46 of BRCA1 and 286 of BRCA2). From them, 256 were distinct VUS (37 in BRCA1 and 219 in BRCA2). Breast cancer sub-classification were collected from medical records and in silico analyzes were performed using four software (SIFT, Polyphen2, CADD and REVEL). Based on this analysis, VUS were categorized into five classes: very high, high, medium, low and very low risk of pathogenicity, according to agreement level among the four in silico software. However, all these analysis are not sufficient for supporting the reclassification of VUS. Therefore we proposed to analyze LoH in matched tumor tissue to assess the pathogenic potential of BRCA1 and 2 VUS. Normal (leucocytes or normal breast tumor tissue) samples, when available, were used for correcting PCR amplification bias between the two alleles. DNA was extracted and subjected to PCR reaction. Amplicons libraries were performed according to manufacturing protocol (Ion Plus Fragment Library Kit) and sequenced on the Ion Proton™ System (ThermoFisher Scientific). Specific variants were called in the TVC program (ThermoFisher Scientific) with standard criteria. A total of 12 VUS were investigated (5 in BRCA1 and 7 in BRCA2). LoH was detected in 7 (60%) tumor samples (3 in BRCA1 and 4 in BRCA2). Of these, 4 VUS were classified as very high or high risk of pathogenicity [2 in BRCA1 (BR1p.Y1703C; BR1p.S1655P) and 2 in BRCA2 (BR2p.S2670L; BR2p.E3002K)]. Variant of allele frequency (VAF) of 94, 65, 70 and 75%, respectively, were detected in tumor tissues. Additionally, recent functional assays described these 4 VUS as non-functional or deleterious variants showing complete agreement with the current LoH results. According to ACMG guidelines considering all available data, LoH, deleterious function and concordant pathogenicity probability. These 4 VUS might be reclassified as pathogenic variants. On the other hand, the same combined analysis did not allow reclassification of 3 other VUS. Although VAF were 74, 73 and 70% respectively, they were previously classified as very or low risk of pathogenicity and there are no functional assays describing them until now. Our results showed that LoH analyses can substantially contribute to VUS reclassification, improving the management and counseling of BRCA1/2 VUS-carriers. Citation Format: Dirce M Carraro, Edenir I Palmero, Carolina M Berra, Giovana T Torrezan, Rafael C Brianese, Gabriela C Fernandes, Angelica M Gutierrez Barrera, Henrique C Galvo, Maria NC Formiga, Banu K Arun. Reclassification of variant of unknown significance in BRCA1 and BRCA2 genes based on loss of heterozigosity assay [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-09-04." @default.
• W3011105220 created "2020-03-23" @default.
• W3011105220 creator A5015127974 @default.
• W3011105220 creator A5017149694 @default.
• W3011105220 creator A5026777870 @default.
• W3011105220 creator A5055599023 @default.
• W3011105220 creator A5057283889 @default.
• W3011105220 creator A5057653111 @default.
• W3011105220 creator A5058001177 @default.
• W3011105220 creator A5060114190 @default.
• W3011105220 creator A5066723346 @default.
• W3011105220 creator A5084699825 @default.
• W3011105220 date "2020-02-14" @default.
• W3011105220 modified "2023-10-18" @default.
• W3011105220 title "Abstract P2-09-04: Reclassification of variant of unknown significance in BRCA1 and BRCA2 genes based on loss of heterozigosity assay" @default.
• W3011105220 doi "https://doi.org/10.1158/1538-7445.sabcs19-p2-09-04" @default.
• W3011105220 hasPublicationYear "2020" @default.
• W3011105220 type Work @default.
• W3011105220 sameAs 3011105220 @default.
• W3011105220 citedByCount "0" @default.
• W3011105220 crossrefType "proceedings-article" @default.
• W3011105220 hasAuthorship W3011105220A5015127974 @default.
• W3011105220 hasAuthorship W3011105220A5017149694 @default.
• W3011105220 hasAuthorship W3011105220A5026777870 @default.
• W3011105220 hasAuthorship W3011105220A5055599023 @default.
• W3011105220 hasAuthorship W3011105220A5057283889 @default.
• W3011105220 hasAuthorship W3011105220A5057653111 @default.
• W3011105220 hasAuthorship W3011105220A5058001177 @default.
• W3011105220 hasAuthorship W3011105220A5060114190 @default.
• W3011105220 hasAuthorship W3011105220A5066723346 @default.
• W3011105220 hasAuthorship W3011105220A5084699825 @default.
• W3011105220 hasConcept C104317684 @default.
• W3011105220 hasConcept C121608353 @default.
• W3011105220 hasConcept C126322002 @default.
• W3011105220 hasConcept C143589142 @default.
• W3011105220 hasConcept C143998085 @default.
• W3011105220 hasConcept C180754005 @default.
• W3011105220 hasConcept C2775905019 @default.
• W3011105220 hasConcept C49105822 @default.
• W3011105220 hasConcept C502942594 @default.
• W3011105220 hasConcept C530470458 @default.
• W3011105220 hasConcept C54355233 @default.
• W3011105220 hasConcept C63363279 @default.
• W3011105220 hasConcept C71924100 @default.
• W3011105220 hasConcept C8185291 @default.
• W3011105220 hasConcept C86803240 @default.
• W3011105220 hasConceptScore W3011105220C104317684 @default.
• W3011105220 hasConceptScore W3011105220C121608353 @default.
• W3011105220 hasConceptScore W3011105220C126322002 @default.
• W3011105220 hasConceptScore W3011105220C143589142 @default.
• W3011105220 hasConceptScore W3011105220C143998085 @default.
• W3011105220 hasConceptScore W3011105220C180754005 @default.
• W3011105220 hasConceptScore W3011105220C2775905019 @default.
• W3011105220 hasConceptScore W3011105220C49105822 @default.
• W3011105220 hasConceptScore W3011105220C502942594 @default.
• W3011105220 hasConceptScore W3011105220C530470458 @default.
• W3011105220 hasConceptScore W3011105220C54355233 @default.
• W3011105220 hasConceptScore W3011105220C63363279 @default.
• W3011105220 hasConceptScore W3011105220C71924100 @default.
• W3011105220 hasConceptScore W3011105220C8185291 @default.
• W3011105220 hasConceptScore W3011105220C86803240 @default.
• W3011105220 hasLocation W30111052201 @default.
• W3011105220 hasOpenAccess W3011105220 @default.
• W3011105220 hasPrimaryLocation W30111052201 @default.
• W3011105220 hasRelatedWork W10381122 @default.
• W3011105220 hasRelatedWork W12019937 @default.
• W3011105220 hasRelatedWork W13600379 @default.
• W3011105220 hasRelatedWork W13603561 @default.
• W3011105220 hasRelatedWork W13936927 @default.
• W3011105220 hasRelatedWork W14868149 @default.
• W3011105220 hasRelatedWork W2976006 @default.
• W3011105220 hasRelatedWork W3073281 @default.
• W3011105220 hasRelatedWork W9577182 @default.
• W3011105220 hasRelatedWork W8041353 @default.
• W3011105220 isParatext "false" @default.
• W3011105220 isRetracted "false" @default.
• W3011105220 magId "3011105220" @default.
• W3011105220 workType "article" @default.