Cancer Diagnostics

A total of 7 different BARD1 isoforms were identified in lung and colorectal cancer cells[1],[2]. Structural analysis shows that the BARD1 isoforms expressed in cancers are derived from either differential splicing or from alternative initiation of transcription[3]. A first description of aberrant expression of BARD1 and differentially spliced isoforms was for breast and ovarian cancer[4],[5]. Aberrant expression of BARD1 correlated with poor prognosis, and repression of BARD1 led to proliferation arrest[1][5].

More recent research has shown that all tissues from 100 NSCLC cases tested express isoform-specific BARD1 epitopes, whilst in lung tissues from healthy controls BARD1 expression is undetectable both on the mRNA and protein levels[1]. Furthermore, the expression of two BARD1 epitopes was significantly correlated with decreased patient survival[1].

Colorectal cancer has been studied in 168 cancer samples[2]. The structure and relative expression of BARD1 mRNA isoforms were further determined in 40 tumour and paired normal peri-tumour tissues. BARD1 isoforms were expressed in 98% of cases and did not correlate with BRCA1. BARD1 mRNA isoforms are upregulated in all tumours as compared with paired normal peri-tumour tissues. Importantly, expression of epitopes mapping to the middle of BARD1 correlate with decreased survival[2]

[1] 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.
[2] 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.
[3] Lepore I, Dell’Aversana D, Pilyugin M, Conte M, Nebbioso A, De Bellis F, Tambaro FP, Izzo T, Garcia-Manero G, Ferrara F, Irminger-Finger I, and Altucci I.  HDAC inhibitors repress BARD1 isoform expression in acute myeloid leukemia cells via activation of miR-19a and/or b. PlosONE 2013, 8(12): e83018.
[4] 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.
[5] 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.