Showing papers by "Jonathan W. Simons published in 2011"
TL;DR: In this paper, the authors presented the complete sequence of seven primary human prostate cancers and their paired normal counterparts and revealed previously unknown balanced rearrangements, at which multiple intra-and inter-chromosomal loci exchange their breakpoint arms without any loss of genetic material.
Abstract: Prostate cancer is the second most common cause of male cancer deaths in the United States. However, the full range of prostate cancer genomic alterations is incompletely characterized. Here we present the complete sequence of seven primary human prostate cancers and their paired normal counterparts. Several tumours contained complex chains of balanced (that is, ‘copy-neutral’) rearrangements that occurred within or adjacent to known cancer genes. Rearrangement breakpoints were enriched near open chromatin, androgen receptor and ERG DNA binding sites in the setting of the ETS gene fusion TMPRSS2–ERG, but inversely correlated with these regions in tumours lacking ETS fusions. This observation suggests a link between chromatin or transcriptional regulation and the genesis of genomic aberrations. Three tumours contained rearrangements that disrupted CADM2, and four harboured events disrupting either PTEN (unbalanced events), a prostate tumour suppressor, or MAGI2 (balanced events), a PTEN interacting protein not previously implicated in prostate tumorigenesis. Thus, genomic rearrangements may arise from transcriptional or chromatin aberrancies and engage prostate tumorigenic mechanisms. Prostate cancer is a common cause of male cancer-related deaths. Complete genome sequencing of seven 'high-risk' primary prostate cancers and their paired normal counterparts now reveals previously unknown balanced rearrangements, at which multiple intra- and inter-chromosomal loci exchange their breakpoint arms without any loss of genetic material. The anomalies seem to arise through errors in transcription or abnormal chromatin structure, and genes affected include the known prostate tumour suppressor PTEN as well as MAG12, a gene not previously implicated in prostate tumorigenesis. Prostate cancer is a common cause of male cancer-related deaths. Complete sequencing of prostate cancer genomes now reveals previously unknown balanced rearrangements. Single-nucleotide resolution afforded by sequencing indicates that complex rearrangements may arise from transcriptional or chromatin aberrancies and engage prostate tumorigenic mechanisms.
1,189 citations
TL;DR: This report highlights some of the most significant advances made in prostate cancer research in 2010 that were presented at the 17th Annual PCF Scientific Retreat.
Abstract: Annually the Prostate Cancer Foundation (PCF) organizes a scientific retreat to assemble the premier prostate cancer researchers from around the world to share and review the latest progress made in the field and to evaluate future directions. This report highlights some of the most significant advances made in prostate cancer research in 2010 that were presented at the 17th Annual PCF Scientific Retreat.
2 citations