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

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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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, VIC, 3010, Australia

    Maryam Mahmoodi, Tu Nguyen-Dumont, Fleur Hammet, Daniel J. Park & Melissa C. Southey

  2. Victorian Life Sciences Computation Initiative, Melbourne, VIC, 3010, Australia

    Bernard J. Pope & Daniel J. Park

  3. Department of Computing and Information Systems, The University of Melbourne, Melbourne, VIC, 3010, Australia

    Bernard J. Pope

  4. Department of Clinical Genetics, Our Lady’s Children’s Hospital, Crumlin, Dublin, 12, Ireland

    John M. Darlow

  5. National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin, Dublin, 12, Ireland

    John M. Darlow

  6. Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia

    Fiona Bruinsma

  7. Department of Medicine, The Universityof Melbourne, Melbourne, Australia

    Ingrid Winship

  8. The Royal Melbourne Hospital, Melbourne, VIC, 3050, Australia

    Ingrid Winship

Authors
  1. Maryam Mahmoodi
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  2. Tu Nguyen-Dumont
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  3. Fleur Hammet
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  4. Bernard J. Pope
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  5. Daniel J. Park
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  6. Melissa C. Southey
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  7. John M. Darlow
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  8. Fiona Bruinsma
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  9. Ingrid Winship
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Corresponding author

Correspondence to Tu Nguyen-Dumont.

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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

Additional information

Maryam Mahmoodi and Tu Nguyen-Dumont contributed equally to this work.

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Mahmoodi, M., Nguyen-Dumont, T., Hammet, F. et al. Mutation screening of ACKR3 and COPS8 in kidney cancer cases from the CONFIRM study. Familial Cancer 16, 411–416 (2017). https://doi.org/10.1007/s10689-016-9961-x

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  • DOI: https://doi.org/10.1007/s10689-016-9961-x

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