Mutation screening of ACKR3 and COPS8 in kidney cancer cases from the CONFIRM study
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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.
KeywordsKidney cancer ACKR3 COPS8 Mutation screening Massively parallel sequencing Hi-Plex
TN-D was a Susan G. Komen for the Cure Postdoctoral Fellow. MCS is a National Health and Medical Research Council Senior Research Fellow. This work was supported by the Australian National Health and Medical Research Council (NHMRC) (APP1025879), Cancer Council Victoria APP1066612 and by a Victorian Life Sciences Computation Initiative (VLSCI) grant (Number VR0182) on its Peak Computing Facility, an initiative of the Victorian Government.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethics approval was granted by the Human Research Ethics Committee of the Cancer Council of Victoria.
Informed consent was obtained from all participants included in the study
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