title: Mutation screening of ACKR3 and COPS8 in kidney cancer cases from the CONFIRM study.
abstract: An apparently balanced t(2;3)(q37.3;q13.2) translocation that appears to segregate with renal cell carcinoma (RCC) has indicated potential areas to search for the elusive genetic basis of clear cell RCC. We applied Hi-Plex targeted sequencing to analyse germline DNA from 479 individuals affected with clear cell RCC for this breakpoint translocation and genetic variants in neighbouring genes on chromosome 2, ACKR3 and COPS8. While only synonymous variants were found in COPS8, one of the missense variants in ACKR3:c.892C>T, observed in 4/479 individuals screened (0.8%), was predicted likely to damage ACKR3 function. Identification of causal genes for RCC has potential clinical utility, where risk assessment and risk management can offer better outcomes, with surveillance for at-risk relatives and nephron sparing surgery through earlier intervention.
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, VIC, 3010, Australia.
authors.forename: Maryam
authors.initials: M
authors.lastname: Mahmoodi
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, VIC, 3010, Australia. tun@unimelb.edu.au.
authors.forename: Tu
authors.initials: T
authors.lastname: Nguyen-Dumont
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, VIC, 3010, Australia.
authors.forename: Fleur
authors.initials: F
authors.lastname: Hammet
authors.affiliation: Victorian Life Sciences Computation Initiative, Melbourne, VIC, 3010, Australia.|Department of Computing and Information Systems, The University of Melbourne, Melbourne, VIC, 3010, Australia.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Pope
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, VIC, 3010, Australia.|Victorian Life Sciences Computation Initiative, Melbourne, VIC, 3010, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Park
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, VIC, 3010, Australia.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.affiliation: Department of Clinical Genetics, Our Lady's Children's Hospital, Crumlin, Dublin, 12, Ireland.|National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, 12, Ireland.
authors.forename: John M
authors.initials: JM
authors.lastname: Darlow
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: Bruinsma
authors.affiliation: Department of Medicine, The Universityof Melbourne, Melbourne, Australia.|The Royal Melbourne Hospital, Melbourne, VIC, 3050, Australia.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Winship
mesh_terms: D000328:Adult; D000075686:COP9 Signalosome Complex / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics*; D054387:Receptors, CXCR / Q000235:genetics*
chemical_list: C501896:ACKR3 protein, human; C579058:COPS8 protein, human; D011506:Proteins; D054387:Receptors, CXCR; D000075686:COP9 Signalosome Complex
keywords: ACKR3; COPS8; Hi-Plex; Kidney cancer; Massively parallel sequencing; Mutation screening