Familial Cancer

, Volume 12, Issue 4, pp 587–595 | Cite as

The incidence of PALB2 c.3113G>A in women with a strong family history of breast and ovarian cancer attending familial cancer centres in Australia

  • Zhi L. Teo
  • Sarah D. Sawyer
  • Paul A. James
  • Gillian Mitchell
  • Alison H. Trainer
  • Geoffrey J. Lindeman
  • Kylie Shackleton
  • Linda Cicciarelli
  • Melissa C. Southey
Letter to the Editor


The familial aggregation of breast cancer has been well-described with approximately 25 % of breast cancers attributable to inherited mutations in currently known breast cancer susceptibility genes. PALB2 c.3113G>A (p.Trp1038*) is a protein-truncating mutation which has been associated with high estimated risk of breast cancer in Australian women (91 %; 95 % CI = 44–100) to age 70 years. This study screened for PALB2 c.3113G>A in germline DNA representing 871 unrelated individuals from “high-risk” breast and/or ovarian cancer families evaluated in the setting of a Familial Cancer Centre in Australia. The PALB2 c.3113G>A mutation was identified in eight of 871 probands (0.92 %) from these families. Median age of diagnosis was 42 years. Five of these eight women had contra-lateral breast cancers. Available data suggests that PALB2 c.3113G>A is a rare mutation with estimated breast cancer risks similar in magnitude to that associated with BRCA2 mutations. Although the proportion of high-risk women carrying this PALB2 mutation is low, research efforts should continue in order to effect its translation into clinical genetic testing practice.


PALB2 Hereditary breast cancer Familial cancer centre BRCA1 and BRCA2 mutation negative 



Familial cancer centre


Victorian familial breast cancer cohort


Whole genome amplified


Estrogen receptor


Progesterone receptor


Human epidermal growth factor-2


Multiplex ligation-dependent probe amplification



This study was supported by the Victorian Cancer Agency (CTTS07, EOI09-50); the National Health and Medical Research Council (NHMRC) via project grant APP1029974, Senior Research Fellowship (M.C.S.), Dora Lush Postgraduate Scholarship (Z.L.T.), Principal Research Fellowship (G.J.L.) and IRIISS; University of Melbourne, Postgraduate Faculty Research Scholarship (Z.L.T.) and the Victorian Breast Cancer Research Consortium and Operational Infrastructure Support. M.C.S. and G.J.L are Victorian Breast Cancer Research Consortium Group Leaders. We wish to thank A/Prof Ian Campbell and the VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre for their assistance with the preparation of the DNA samples (Victorian Breast Cancer Research Consortium). We also thank Prof Ingrid Winship for her contribution and critical assessment of the manuscript. The authors gratefully acknowledge the contribution of the staff at the Familial Cancer centres who assisted in the annotation of the families and the staff of the Genetic Epidemiology Laboratory who supported aspects of the bench work.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Zhi L. Teo
    • 1
  • Sarah D. Sawyer
    • 2
  • Paul A. James
    • 2
    • 3
  • Gillian Mitchell
    • 2
    • 3
  • Alison H. Trainer
    • 2
    • 4
  • Geoffrey J. Lindeman
    • 4
    • 5
    • 6
  • Kylie Shackleton
    • 4
  • Linda Cicciarelli
    • 2
  • Melissa C. Southey
    • 1
  1. 1.Genetic Epidemiology Laboratory, Department of PathologyThe University of MelbourneMelbourneAustralia
  2. 2.Familial Cancer CentreThe Peter MacCallum Cancer CentreEast MelbourneAustralia
  3. 3.The Sir Peter MacCallum Department of OncologyThe University of MelbourneMelbourneAustralia
  4. 4.Familial Cancer CentreThe Royal Melbourne HospitalParkvilleAustralia
  5. 5.The Walter and Eliza Hall Institute of Medical ResearchParkvilleAustralia
  6. 6.The Department of MedicineThe University of MelbourneMelbourneAustralia

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