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
  • 138 Downloads

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.

Keywords

Kidney cancer ACKR3 COPS8 Mutation screening Massively parallel sequencing Hi-Plex 

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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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