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Paper Review #1
"The genomic complexity of primary human prostate cancer"
Berger, et al., 2011
- Prostate cancer causes the second highest number of male cancer deaths in the United States.
- The complete range of prostate cancer genomic alterations is not fully understood.
- Androgen (male steroid hormone) deprivation therapy is a common treatment option, but the majority of metastatic prostate cancer patients end up dying because of the cancer. Thus, the need to characterize underlying genetic factors and novel therapeutic targets in prostate cancer remains.
- This study represents the first whole genome sequencing analysis of human prostate cancer.
- Prior to this study, systematic genome characterization efforts have often focused primarily on gene-coding regions to identify ‘driver’ or ‘druggable’ alterations. Whole genome sequencing data indicate that complex chromosomal rearrangements may lead to significant gain- and loss-of-function driver events in primary prostate carcinogenesis.
- Researchers sequenced the complete genomes of seven prostate tumors and patient-matched normal samples to about 30-fold haploid coverage using an Ilumina GA II sequencer.
- The DNA was obtained from tumors after surgical removal of prostates as well as from patient blood. Quality control measures were utilized.
- Researchers sequenced standard paired-end libraries (about 400-base pair inserts) as 101-base pair paired-end reads.
- Illumina software was used to align the raw sequencing data to the reference genome.
- The Firehose pipeline was used to analyze each tumor/normal sample pair, thereby characterizing the full spectrum of somatic mutations in each tumor.
- FISH (fluorescence in situ hybridization) was performed for selected recurrent rearrangements, followed by reverse transcriptase-PCR.
- Previously published ChIP binding peaks from related cell types were used as a reference for comparing the locations of all rearrangement breakpoints, thereby testing for universal associations between rearrangements and a range of epigenetic (heritable phenotype differences not caused by the underlying DNA sequence) marks.
Berger MF, Lawrence MS, Demichelis F, Drier Y, Cibulskis K, Sivachenko AY, Sboner A, Esgueva R, Pflueger D, Sougnez C, et al. The genomic complexity of primary human prostate cancer. Nature [Internet]. 2011 Feb 10 [cited 2011 Feb 21];470(7333): 214-220. Available from: http://www.nature.com/nature/journal/v470/n7333/full/nature09744.html
*Note: All citable information was taken from this original paper.
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