Scientific Rationale

BARD1 is potentially both a diagnostic biomarker and therapeutic target for cancer.

Diagnostic Biomarker

BARD1 protein has important properties that make it attractive for cancer diagnosis:

  • Aberrant BARD1 proteins are released (ie outside the cell body) by cancer cells, and give rise to the generation of circulating antibodies. These circulating antibodies are present early in the blood and are therefore easily accessible markers of cancer.
  • BARD1 epitopes are immunogenic[5] and BARD1’s diagnostic tests exploit the presence of these circulating antibodies, which serve as “biomarkers” for the announcement and progression of cancer cells.
  • BARD1 cancer-specific RNA-isoforms are generated by alternate splicing of the BARD1 gene[1][4]. This leads to RNA-based “signatures” that are diagnostic of cancer. These can be addressed in liquid biopsies by analysing Circulating Tumour Cells (CTC) and/or circulating RNA.

 

Therapeutic Target

The oncogenic capacity of cancer-associated BARD1 isoforms makes them potential therapeutic targets that can be addressed using inhibitory approaches based on small interfering RNAs, anti-BARD1 antibodies, or other methods enabling targeted therapies for prevention or treatment of cancer.

[1] Wu, J.Y., A.T. Vlastos, M.F. Pelte, M.A. Caligo, A. Bianco, K.H. Krause, G.J. Laurent, and I. Irminger-Finger. 2006. Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis. Int J Cancer 118: 1215-26.
[2] Li, L., S. Ryser, E. Dizin, D. Pils, M. Krainer, C.E. Jefford, F. Bertoni, R. Zeillinger, and I. Irminger-Finger. 2007b. Oncogenic BARD1 isoforms expressed in gynecological cancers. Cancer Res 67: 11876-85.
[3]  Zhang YQ, Bianco A, Malkinson AM, Leoni VP, Frau G, De Rosa N, André PA, Versace R, Boulvain M, Laurent GJ, Atzori L, Irminger-Finger I. 2012. BARD1: an independent predictor of survival in non-small cell lung cancer. Int J Cancer. 131(1):83-94.
[4] Zhang YQ, Pilyugin M, Kuester D, Leoni VP, Li L, Casula G, Zorcolo L, Schneider-Stock R, Atzori L, Irminger-Finger I. 2012. Expression of oncogenic BARD1 isoforms affects colon cancer progression and correlates with clinical outcome. Br J Cancer 107:675-83.
[5] Gautier, F., I. Irminger-Finger, M. Gregoire, K. Meflah, and J. Harb. 2000. Identification of an apoptotic cleavage product of BARD1 as an autoantigen: a potential factor in the antitumoural response mediated by apoptotic bodies. Cancer Res 60: 6895-900.