Familial Cancer

, Volume 16, Issue 3, pp 411–416 | Cite as

Mutation screening of ACKR3 and COPS8 in kidney cancer cases from the CONFIRM study

  • Maryam Mahmoodi
  • Tu Nguyen-Dumont
  • Fleur Hammet
  • Bernard J. Pope
  • Daniel J. Park
  • Melissa C. Southey
  • John M. Darlow
  • Fiona Bruinsma
  • Ingrid Winship
Original Article


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.


Kidney 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.

Ethical approval

Ethics approval was granted by the Human Research Ethics Committee of the Cancer Council of Victoria.

Informed consent

Informed consent was obtained from all participants included in the study


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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Maryam Mahmoodi
    • 1
  • Tu Nguyen-Dumont
    • 1
  • Fleur Hammet
    • 1
  • Bernard J. Pope
    • 2
    • 3
  • Daniel J. Park
    • 1
    • 2
  • Melissa C. Southey
    • 1
  • John M. Darlow
    • 4
    • 5
  • Fiona Bruinsma
    • 6
  • Ingrid Winship
    • 7
    • 8
  1. 1.Genetic Epidemiology Laboratory, Department of PathologyThe University of MelbourneMelbourneAustralia
  2. 2.Victorian Life Sciences Computation InitiativeMelbourneAustralia
  3. 3.Department of Computing and Information SystemsThe University of MelbourneMelbourneAustralia
  4. 4.Department of Clinical GeneticsOur Lady’s Children’s HospitalDublinIreland
  5. 5.National Children’s Research CentreOur Lady’s Children’s HospitalDublinIreland
  6. 6.Cancer Epidemiology CentreCancer Council VictoriaMelbourneAustralia
  7. 7.Department of MedicineThe Universityof MelbourneMelbourneAustralia
  8. 8.The Royal Melbourne HospitalMelbourneAustralia

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