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The diverse heterogeneity of molecular alterations in prostate cancer identified through next-generation sequencing

Asian Journal of Andrology 2013年第3期15卷 301-308页

作者： Alexander W Wyatt Fan Mo Yuzhuo Wang Colin C Collins Vancouver prostate Centre & Department of Urologic Sciences University of British Columbia Vancouver BC V6H 3Z6 Canada Department of Experimental Therapeutics BC Cancer Agency Vancouver BC VSZ 1L3 Canada

prostate cancer is a leading cause of global cancer-related death but attempts to improve diagnoses and develop novel therapies have been confounded by significant patient heterogeneity. In recent years, the application of next-generation sequencing to hundreds of prostate tumours has defined novel molecular subtypes and characterized extensive genomic aberration underlying disease initiation and progression. It is now clear that the heterogeneity observed in the clinic is underpinned by a molecular landscape rife with complexity, where genomic rearrangements and rare mutations combine to amplify transcriptomic diversity. This review dissects our current understanding of prostate cancer ＇omics＇, including the sentinel role of copy number variation, the growing spectrum of oncogenic fusion genes, the potential influence of chromothripsis, and breakthroughs in defining mutation-associated subtypes. Increasing evidence suggests that genomic lesions frequently converge on specific cellular functions and signalling pathways, yet recurrent gene aberration appears rare. Therefore, it is critical that we continue to define individual tumour genomes, especially in the context of their expressed transcriptome. Only through improved characterisation of tumour to tumour variability can we advance to an age of precision therapy and personalized oncology.

关键词： cancer sequencing copy number fusion gene genome genome rearrangement personalized oncology prostate cancer transcriptome

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