Clinical School (Austin Health) - Research Publications

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    Advances in ureteroscopy
    Wetherell, DR ; Ling, D ; Ow, D ; Koonjbeharry, B ; Sliwinski, A ; Weerakoon, M ; Papa, N ; Lawrentschuk, N ; Bolton, DM (AME PUBL CO, 2014-09-01)
    Ureteroscopy (URS) is a procedure which has been constantly evolving since the development of first generation devices 40 years ago. Progress towards smaller and more sophisticated equipment has been particularly rapid in the last decade. We review the significant steps that have been made toward improving outcomes and limiting morbidity with this procedure which is central to the management of urolithiasis and other upper urinary tract pathology.
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    Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories
    Taylor, RA ; Fraser, M ; Livingstone, J ; Espiritu, SMG ; Thorne, H ; Huang, V ; Lo, W ; Shiah, Y-J ; Yamaguchi, TN ; Sliwinski, A ; Horsburgh, S ; Meng, A ; Heisler, LE ; Yu, N ; Yousif, F ; Papargiris, M ; Lawrence, MG ; Timms, L ; Murphy, DG ; Frydenberg, M ; Hopkins, JF ; Bolton, D ; Clouston, D ; McPherson, JD ; van der Kwast, T ; Boutros, PC ; Risbridger, GP ; Bristow, RG (NATURE PUBLISHING GROUP, 2017-01-09)
    Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and increased risk of aggressive disease. To understand this aggression, here we profile the genomes and methylomes of localized PCa from 14 carriers of deleterious germline BRCA2 mutations (BRCA2-mutant PCa). We show that BRCA2-mutant PCa harbour increased genomic instability and a mutational profile that more closely resembles metastastic than localized disease. BRCA2-mutant PCa shows genomic and epigenomic dysregulation of the MED12L/MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer (mCRPC). This dysregulation is enriched in BRCA2-mutant PCa harbouring intraductal carcinoma (IDC). Microdissection and sequencing of IDC and juxtaposed adjacent non-IDC invasive carcinoma in 10 patients demonstrates a common ancestor to both histopathologies. Overall we show that localized castration-sensitive BRCA2-mutant tumours are uniquely aggressive, due to de novo aberration in genes usually associated with metastatic disease, justifying aggressive initial treatment.