Matches in SemOpenAlex for { <https://semopenalex.org/work/W2964498052> ?p ?o ?g. }
Showing items 1 to 86 of
86
with 100 items per page.
- W2964498052 abstract "10521 Background: Uveal melanoma (UM) is a rare malignancy with a poor prognosis. Familial predisposition to UM is rare and accounts for only a few percent of all cases. The genetic background of hereditary UM is unknown and the aim of our project was to identify susceptibility gene(s) for UM. Methods: We identified a family with hereditary predisposition for UM – the proband of which is a young female diagnosed with UM at age 16 who within 6 months developed liver metastases. We also identified two older paternal relatives who were diagnosed with UM at 39 and 44 years of age, respectively. We performed massively parallel sequencing using the Illumina Hiseq2000 technology on germline DNA from the proband, her parents and a healthy sibling. After QC and mapping against the human reference genome the average coverage across the exome was between 35 and 86 for the four sequenced samples. Results: Out of more than 260,000 single nucleotide variants (SNVs) and small insertion / deletion variants (indels), 51 gene variants were filtered out by being novel, shared by the affected proband and her father (considered an obligate mutation carrier), but not by the healthy mother, of predicted functional importance and /or located within strongly conserved regions. The strongest candidate among these was a loss of function-variant in the BAP1 gene, since BAP1 has been suggested as a tumor suppressor in several cancer-related syndromes, including cases of UM. The sequence data indicated an insertion of one base-pair in exon 3 of the BAP1 genecausing a frame-shift and subsequently a truncated protein lacking all its functional domains. The mutation was also present in UM tumor tissue from the two deceased paternal relatives and was found to segregate with the UM phenotype in the family. We also detected loss of heterozygosity in the tumor of the proband, supporting BAP1 as the causative gene in this family. Conclusions: The identification of BAP1 as the gene responsible for this syndrome is the first demonstration of a germline mutation causing UM. This enables us to identify and monitor risk individuals belonging to mutation positive families with predisposition to UM, and possibly other cancer syndromes. We are continuously screening other cases of familial UM for mutations in BAP1." @default.
- W2964498052 created "2019-08-13" @default.
- W2964498052 creator A5006758671 @default.
- W2964498052 creator A5024889166 @default.
- W2964498052 creator A5030567606 @default.
- W2964498052 creator A5052059834 @default.
- W2964498052 creator A5054656710 @default.
- W2964498052 creator A5055025766 @default.
- W2964498052 creator A5057409863 @default.
- W2964498052 creator A5062882825 @default.
- W2964498052 creator A5071927003 @default.
- W2964498052 date "2012-05-20" @default.
- W2964498052 modified "2023-09-30" @default.
- W2964498052 title "BAP1: The first mutated gene causing familial uveal melanoma." @default.
- W2964498052 doi "https://doi.org/10.1200/jco.2012.30.15_suppl.10521" @default.
- W2964498052 hasPublicationYear "2012" @default.
- W2964498052 type Work @default.
- W2964498052 sameAs 2964498052 @default.
- W2964498052 citedByCount "0" @default.
- W2964498052 crossrefType "journal-article" @default.
- W2964498052 hasAuthorship W2964498052A5006758671 @default.
- W2964498052 hasAuthorship W2964498052A5024889166 @default.
- W2964498052 hasAuthorship W2964498052A5030567606 @default.
- W2964498052 hasAuthorship W2964498052A5052059834 @default.
- W2964498052 hasAuthorship W2964498052A5054656710 @default.
- W2964498052 hasAuthorship W2964498052A5055025766 @default.
- W2964498052 hasAuthorship W2964498052A5057409863 @default.
- W2964498052 hasAuthorship W2964498052A5062882825 @default.
- W2964498052 hasAuthorship W2964498052A5071927003 @default.
- W2964498052 hasConcept C104317684 @default.
- W2964498052 hasConcept C126322002 @default.
- W2964498052 hasConcept C143998085 @default.
- W2964498052 hasConcept C16005928 @default.
- W2964498052 hasConcept C2777658100 @default.
- W2964498052 hasConcept C2779134260 @default.
- W2964498052 hasConcept C2779176653 @default.
- W2964498052 hasConcept C2779399171 @default.
- W2964498052 hasConcept C37846818 @default.
- W2964498052 hasConcept C501734568 @default.
- W2964498052 hasConcept C502942594 @default.
- W2964498052 hasConcept C54355233 @default.
- W2964498052 hasConcept C67636389 @default.
- W2964498052 hasConcept C71924100 @default.
- W2964498052 hasConcept C86803240 @default.
- W2964498052 hasConceptScore W2964498052C104317684 @default.
- W2964498052 hasConceptScore W2964498052C126322002 @default.
- W2964498052 hasConceptScore W2964498052C143998085 @default.
- W2964498052 hasConceptScore W2964498052C16005928 @default.
- W2964498052 hasConceptScore W2964498052C2777658100 @default.
- W2964498052 hasConceptScore W2964498052C2779134260 @default.
- W2964498052 hasConceptScore W2964498052C2779176653 @default.
- W2964498052 hasConceptScore W2964498052C2779399171 @default.
- W2964498052 hasConceptScore W2964498052C37846818 @default.
- W2964498052 hasConceptScore W2964498052C501734568 @default.
- W2964498052 hasConceptScore W2964498052C502942594 @default.
- W2964498052 hasConceptScore W2964498052C54355233 @default.
- W2964498052 hasConceptScore W2964498052C67636389 @default.
- W2964498052 hasConceptScore W2964498052C71924100 @default.
- W2964498052 hasConceptScore W2964498052C86803240 @default.
- W2964498052 hasLocation W29644980521 @default.
- W2964498052 hasOpenAccess W2964498052 @default.
- W2964498052 hasPrimaryLocation W29644980521 @default.
- W2964498052 hasRelatedWork W102540197 @default.
- W2964498052 hasRelatedWork W1547269319 @default.
- W2964498052 hasRelatedWork W2004370760 @default.
- W2964498052 hasRelatedWork W2008981153 @default.
- W2964498052 hasRelatedWork W2025106928 @default.
- W2964498052 hasRelatedWork W2047777235 @default.
- W2964498052 hasRelatedWork W2079853337 @default.
- W2964498052 hasRelatedWork W2086089386 @default.
- W2964498052 hasRelatedWork W2117596181 @default.
- W2964498052 hasRelatedWork W2147450167 @default.
- W2964498052 hasRelatedWork W219740331 @default.
- W2964498052 hasRelatedWork W2283948722 @default.
- W2964498052 hasRelatedWork W2285588397 @default.
- W2964498052 hasRelatedWork W2440525104 @default.
- W2964498052 hasRelatedWork W2519075935 @default.
- W2964498052 hasRelatedWork W2559513803 @default.
- W2964498052 hasRelatedWork W2770563388 @default.
- W2964498052 hasRelatedWork W2885273470 @default.
- W2964498052 hasRelatedWork W3081794867 @default.
- W2964498052 hasRelatedWork W3208948747 @default.
- W2964498052 isParatext "false" @default.
- W2964498052 isRetracted "false" @default.
- W2964498052 magId "2964498052" @default.
- W2964498052 workType "article" @default.