<> <http://www.w3.org/2000/01/rdf-schema#comment> "The repository administrator has not yet configured an RDF license."^^<http://www.w3.org/2001/XMLSchema#string> .
<> <http://xmlns.com/foaf/0.1/primaryTopic> <https://discovery.ucl.ac.uk/id/eprint/10090009> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/AcademicArticle> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Article> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/title> "Role for Nucleotide Excision Repair Gene Variants in Oxaliplatin-Induced Peripheral Neuropathy"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/abstract> "Purpose:\r\nOxaliplatin forms part of routine treatment of advanced colorectal cancer; however, it often causes severe peripheral neuropathy, resulting in treatment discontinuation. We sought to determine the molecular and cellular mechanism underlying this toxicity. /\r\n\r\nPatients and Methods:\r\nWe exome resequenced blood DNA samples from nine patients with advanced colorectal cancer who had severe peripheral neuropathy associated with oxaliplatin (PNAO) within 12 weeks of treatment. We Sanger sequenced the ERCC4 and ERCC6 open reading frames in 63 patients with PNAO and carried out targeted genotyping in 1,763 patients without PNAO. We tested the functionality of ERCC4 variants using viability and DNA repair assays in Schizosaccharomyces pombe and human cell lines after exposure to oxaliplatin and ultraviolet light. /\r\n\r\nResults:\r\nExome resequencing identified one patient carrying a novel germline truncating mutation in the nucleotide excision repair (NER) gene ERCC4. This mutation was functionally associated with sensitivity to oxaliplatin (P = 3.5 × 10−2). We subsequently found that multiple rare ERCC4 nonsynonymous variants were over-represented in affected individuals (P = 7.7 × 10−3) and three of these were defective in the repair of ultraviolet light–induced DNA damage (P < 1 × 10−3). We validated a role for NER genes in PNAO by finding that multiple rare ERCC6 nonsynonymous variants were similarly over-represented in affected individuals (P = 2.4 × 10−8). Excluding private variants, 22.2% of patients (14 of 63 patients) with PNAO carried Pro379Ser or Glu875Gly in ERCC4 or Asp425Ala, Gly446Asp, or Ser797Cys in ERCC6, compared with 8.7% of unaffected patients (152 of 1,750 patients; odds ratio, 3.0; 95% CI, 1.6 to 5.6; P = 2.5 × 10−4). /\r\n\r\nConclusion: \r\nOur study provides evidence for a role of NER genes in PNAO, together with mechanistic insights."^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/date> "2018-10-10" .
<https://discovery.ucl.ac.uk/id/document/1039886> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Document> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/volume> "2" .
<https://discovery.ucl.ac.uk/id/publication/ext-24734284> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Collection> .
<https://discovery.ucl.ac.uk/id/publication/ext-24734284> <http://xmlns.com/foaf/0.1/name> "JCO Precision Oncology"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/isPartOf> <https://discovery.ucl.ac.uk/id/publication/ext-24734284> .
<https://discovery.ucl.ac.uk/id/publication/ext-24734284> <http://www.w3.org/2002/07/owl#sameAs> <urn:issn:24734284> .
<https://discovery.ucl.ac.uk/id/publication/ext-24734284> <http://purl.org/ontology/bibo/issn> "24734284" .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/status> <http://purl.org/ontology/bibo/status/forthcoming> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-0bdaee1fd6af22b473e3332e61d9032b> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10090009#authors> .
<https://discovery.ucl.ac.uk/id/eprint/10090009#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_1> <https://discovery.ucl.ac.uk/id/person/ext-0bdaee1fd6af22b473e3332e61d9032b> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-078e6dd438b7dfd8bb00483cc276934f> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10090009#authors> .
<https://discovery.ucl.ac.uk/id/eprint/10090009#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_2> <https://discovery.ucl.ac.uk/id/person/ext-078e6dd438b7dfd8bb00483cc276934f> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-93ff6878b83f455c19bab49047911a98> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10090009#authors> .
<https://discovery.ucl.ac.uk/id/eprint/10090009#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_3> <https://discovery.ucl.ac.uk/id/person/ext-93ff6878b83f455c19bab49047911a98> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-0fadf8b283c3479dae736c1e006d8b28> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10090009#authors> .
<https://discovery.ucl.ac.uk/id/eprint/10090009#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_4> <https://discovery.ucl.ac.uk/id/person/ext-0fadf8b283c3479dae736c1e006d8b28> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-8f92f0244609317a125437421d56f8fb> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10090009#authors> .
<https://discovery.ucl.ac.uk/id/eprint/10090009#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_5> <https://discovery.ucl.ac.uk/id/person/ext-8f92f0244609317a125437421d56f8fb> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-8e2ed8efbb93430cd50c980ef8f68e7d> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10090009#authors> .
<https://discovery.ucl.ac.uk/id/eprint/10090009#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_6> <https://discovery.ucl.ac.uk/id/person/ext-8e2ed8efbb93430cd50c980ef8f68e7d> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-5d623d198b8f4c101a039d2327cd88a7> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10090009#authors> .
<https://discovery.ucl.ac.uk/id/eprint/10090009#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_7> <https://discovery.ucl.ac.uk/id/person/ext-5d623d198b8f4c101a039d2327cd88a7> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-32a7e1106c7b86c120564fddf9abc82f> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10090009#authors> .
<https://discovery.ucl.ac.uk/id/eprint/10090009#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_8> <https://discovery.ucl.ac.uk/id/person/ext-32a7e1106c7b86c120564fddf9abc82f> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-c17c1101cbd188fa97d32e4a8795c1db> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10090009#authors> .
<https://discovery.ucl.ac.uk/id/eprint/10090009#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_9> <https://discovery.ucl.ac.uk/id/person/ext-c17c1101cbd188fa97d32e4a8795c1db> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-4eac84837664c972bf900d395f78fe39> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10090009#authors> .
<https://discovery.ucl.ac.uk/id/eprint/10090009#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_10> <https://discovery.ucl.ac.uk/id/person/ext-4eac84837664c972bf900d395f78fe39> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-f0315bf31630ea907d14fd465e4bf582> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10090009#authors> .
<https://discovery.ucl.ac.uk/id/eprint/10090009#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_11> <https://discovery.ucl.ac.uk/id/person/ext-f0315bf31630ea907d14fd465e4bf582> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-cbebd01b0ccc673fd4b9130baebb6926> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10090009#authors> .
<https://discovery.ucl.ac.uk/id/eprint/10090009#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_12> <https://discovery.ucl.ac.uk/id/person/ext-cbebd01b0ccc673fd4b9130baebb6926> .
<https://discovery.ucl.ac.uk/id/person/ext-8e2ed8efbb93430cd50c980ef8f68e7d> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-8e2ed8efbb93430cd50c980ef8f68e7d> <http://xmlns.com/foaf/0.1/givenName> "RA"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-8e2ed8efbb93430cd50c980ef8f68e7d> <http://xmlns.com/foaf/0.1/familyName> "Adams"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-8e2ed8efbb93430cd50c980ef8f68e7d> <http://xmlns.com/foaf/0.1/name> "RA Adams"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-5d623d198b8f4c101a039d2327cd88a7> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-5d623d198b8f4c101a039d2327cd88a7> <http://xmlns.com/foaf/0.1/givenName> "O"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-5d623d198b8f4c101a039d2327cd88a7> <http://xmlns.com/foaf/0.1/familyName> "Fleck"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-5d623d198b8f4c101a039d2327cd88a7> <http://xmlns.com/foaf/0.1/name> "O Fleck"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-0bdaee1fd6af22b473e3332e61d9032b> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-0bdaee1fd6af22b473e3332e61d9032b> <http://xmlns.com/foaf/0.1/givenName> "H"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-0bdaee1fd6af22b473e3332e61d9032b> <http://xmlns.com/foaf/0.1/familyName> "West"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-0bdaee1fd6af22b473e3332e61d9032b> <http://xmlns.com/foaf/0.1/name> "H West"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-cbebd01b0ccc673fd4b9130baebb6926> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-cbebd01b0ccc673fd4b9130baebb6926> <http://xmlns.com/foaf/0.1/givenName> "JP"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-cbebd01b0ccc673fd4b9130baebb6926> <http://xmlns.com/foaf/0.1/familyName> "Cheadle"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-cbebd01b0ccc673fd4b9130baebb6926> <http://xmlns.com/foaf/0.1/name> "JP Cheadle"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-078e6dd438b7dfd8bb00483cc276934f> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-078e6dd438b7dfd8bb00483cc276934f> <http://xmlns.com/foaf/0.1/givenName> "M"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-078e6dd438b7dfd8bb00483cc276934f> <http://xmlns.com/foaf/0.1/familyName> "Coffey"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-078e6dd438b7dfd8bb00483cc276934f> <http://xmlns.com/foaf/0.1/name> "M Coffey"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-8f92f0244609317a125437421d56f8fb> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-8f92f0244609317a125437421d56f8fb> <http://xmlns.com/foaf/0.1/givenName> "JP"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-8f92f0244609317a125437421d56f8fb> <http://xmlns.com/foaf/0.1/familyName> "Colley"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-8f92f0244609317a125437421d56f8fb> <http://xmlns.com/foaf/0.1/name> "JP Colley"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-f0315bf31630ea907d14fd465e4bf582> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-f0315bf31630ea907d14fd465e4bf582> <http://xmlns.com/foaf/0.1/givenName> "R"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-f0315bf31630ea907d14fd465e4bf582> <http://xmlns.com/foaf/0.1/familyName> "Harris"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-f0315bf31630ea907d14fd465e4bf582> <http://xmlns.com/foaf/0.1/name> "R Harris"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-4eac84837664c972bf900d395f78fe39> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-4eac84837664c972bf900d395f78fe39> <http://xmlns.com/foaf/0.1/givenName> "RS"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-4eac84837664c972bf900d395f78fe39> <http://xmlns.com/foaf/0.1/familyName> "Kaplan"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-4eac84837664c972bf900d395f78fe39> <http://xmlns.com/foaf/0.1/name> "RS Kaplan"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-93ff6878b83f455c19bab49047911a98> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-93ff6878b83f455c19bab49047911a98> <http://xmlns.com/foaf/0.1/givenName> "MJ"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-93ff6878b83f455c19bab49047911a98> <http://xmlns.com/foaf/0.1/familyName> "Wagner"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-93ff6878b83f455c19bab49047911a98> <http://xmlns.com/foaf/0.1/name> "MJ Wagner"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-0fadf8b283c3479dae736c1e006d8b28> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-0fadf8b283c3479dae736c1e006d8b28> <http://xmlns.com/foaf/0.1/givenName> "HL"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-0fadf8b283c3479dae736c1e006d8b28> <http://xmlns.com/foaf/0.1/familyName> "McLeod"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-0fadf8b283c3479dae736c1e006d8b28> <http://xmlns.com/foaf/0.1/name> "HL McLeod"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-32a7e1106c7b86c120564fddf9abc82f> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-32a7e1106c7b86c120564fddf9abc82f> <http://xmlns.com/foaf/0.1/givenName> "TS"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-32a7e1106c7b86c120564fddf9abc82f> <http://xmlns.com/foaf/0.1/familyName> "Maughan"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-32a7e1106c7b86c120564fddf9abc82f> <http://xmlns.com/foaf/0.1/name> "TS Maughan"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-c17c1101cbd188fa97d32e4a8795c1db> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-c17c1101cbd188fa97d32e4a8795c1db> <http://xmlns.com/foaf/0.1/givenName> "D"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-c17c1101cbd188fa97d32e4a8795c1db> <http://xmlns.com/foaf/0.1/familyName> "Fisher"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-c17c1101cbd188fa97d32e4a8795c1db> <http://xmlns.com/foaf/0.1/name> "D Fisher"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10090009> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://eprints.org/ontology/EPrint> .
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