Mapping prostate cancer aggressiveness loci

Non-metastatic primary prostate cancers frequently contain multiple independent histologic foci of cancer, and appear as truly multifocal tumors, since these different foci are often genetically distinct (Aihara et al., Urology 43:60-66, 1994; Bostwick et al., Cancer 83:1995-2002,1998; Macintosh et al., Cancer Res 58:23-28, 1998; Mehra et al., Cancer Res 67:7991-7995, 2007; Clark et al., Oncogene 27:1993-2003, 2008). By converse, multiple metastases in the same patient are clonally related, indicating that advanced prostate cancer is monoclonal both at molecular and cytogenetic level (Mehra et al., Cancer Res 68:3584-3590, 2008; Liu et al. 2009). Genomics will hopefully allow the sub-typing of prostate cancer for diagnostic purposes, overcoming the limits of morphology to prognostically evaluate this tumor (Taylor et al., Cancer Cell 18(1):11-22, 2010). The major part of studies searching for genetic variants correlated with prostate cancer, have yielded preferentially results indicating that several genetic loci impact early stages of prostate cancer development. Few data exist, to date, on the existence of loci unequivocally correlated with prostate cancer progression (Liu et al., Front Endocrinol (Lausanne) 3:72, 2012). Recently, however, integrative genomic analysis techniques identified copy number variation as a biomarker predictive of prostate cancer outcome (Ding et al., Nature 470(7333):269-273, 2011), and comparative oncogenomics have derived a four-gene signature and an additional pathway-representative fourteen-gene panel that resulted better prognostic biomarkers with respect to PSA (Ding et al., Nature 470(7333):269-273, 2011). Moreover, the use of a five-SNP panel was found useful to predict the aggressive behavior of prostate cancer (Lin et al., Cancer Epidemiol Biomarkers Prev 20:954-961, 2011). Thus, the advancement of genetic techniques has opened up the promising scenario of a next coming mapping of prostate cancer aggressiveness loc