In conclusion our study has identified a spl http

In conclusion, our study has identified a splice site as 481 (c.1769-1G > C) in the AR gene from two patients with complete androgen insensitivity syndrome. The c.1769-1G > C mutation may provide us new insights into the molecular mechanism involved in splicing defects underlying CAIS. Our findings extend the spectrum of AR mutations and highlight the importance of sequencing splice sites surrounding the exon-intron junctions and the necessary to carry out RNA studies to ensure precise molecular diagnosis. Furthermore, these results may aid in the identification of mutational hot spots, which may be useful in the diagnosis and treatment of this disease.
Disclosure statement
Introduction Despite the high survival rates and recent progress in treatment modalities, prostate cancer (PCa) remains an important healthcare issue with a widespread socio-economic impact (Ferlay et al., 2015). In the majority of cases, PCa is organ-confined at the moment of diagnosis and a cure can be provided by prostatectomy or radiation therapy (>90% progression free survival). However, the more advanced forms of the disease can metastasize, mainly to the bone (90%) or lung (46%) (Chang et al., 2014) and are incurable. The benchmark treatment for metastatic PCa is androgen deprivation therapy (ADT) combined or not with chemotherapy. Unfortunately, in most cases the disease will become resistant to ADT, hence the classification of “castration-resistant prostate cancer” (CRPC). At this stage, hormone therapy with AR-targeting drugs is considered. Unfortunately, although at first these approaches can be effective, the development of resistance is inevitable in most cases (Hotte and Saad, 2010). Development of resistance happens mostly via the reactivation of the AR axis, thus several novel compounds targeting the AR axis have been developed (Andersen et al., 2010, Helsen et al., 2014, Njar and Brodie, 2015). During the progression of metastatic castration resistant prostate cancer (mCRPC), serum PSA measurements and bone scans may provide valuable prognostic information (Cornford et al., 2016), but because they do not report on the underlying mechanisms, their use in the development of personalized precision therapy is limited. To have an idea on the mechanisms that are involved in cancer progression for each individual patient, one would need markers that provide more precise information on the relevant metastases. Unfortunately, sampling multiple metastases or identification of the most relevant metastases is nearly impossible in current clinical practice. One alternative source of information on disease progression could come from liquid biopsies. The term ‘liquid biopsies’ can indicate urine, blood, saliva or even spinal fluids. These can serve as minimally invasive diagnostic sources of information because biomolecules originating from tumor masses leak into the circulation. Like for most cancers, for prostate cancer, blood would be the preferred liquid biopsy because of the ease of collection and reproducible processing modalities. While blood has traditionally been used to follow PSA and other protein and metabolic markers, more recently, it is used as a source of tumor lipids (Butler et al., 2016), RNA (Sita-Lumsden et al., 2013), DNA (Wyatt et al., 2016), exosomes (Bobrie and Théry, 2013) and tumor cells (de Bono et al., 2008). In recent years, circulating tumor DNA (ctDNA) and the circulating tumor cells (CTCs) were added as blood-derived markers. Circulating tumor DNA provides robust information on irreversible changes of the genome in the tumor cells it originates from. CTCs on the other hand can be interrogated not only at the level of their DNA, but also at the level of other biomolecules or signaling pathways. Currently, CTC enumeration by the use of CELLSEARCH® is approved by Food and Drug Administration (FDA) as a means of predicting overall survival in metastatic PCa (de Bono et al., 2008). One caveat here is that it is still not clear which of the molecular changes in CTCs reflect the progression of the disease.