Author/Authors :
Sylvan C. Baca، نويسنده , , Davide Prandi، نويسنده , , Michael S. Lawrence، نويسنده , , Juan Miguel Mosquera، نويسنده , , Alessandro Romanel، نويسنده , , Yotam Drier، نويسنده , , Kyung Park، نويسنده , , Naoki Kitabayashi، نويسنده , , Theresa Y. MacDonald، نويسنده , , Mahmoud Ghandi، نويسنده , , Eliezer Van Allen، نويسنده , , Gregory V. Kryukov، نويسنده , , Andrea Sboner، نويسنده , , Jean-Philippe Theurillat، نويسنده , , T. David Soong، نويسنده , , Elizabeth Nickerson، نويسنده , , Daniel Auclair، نويسنده , , Ashutosh Tewari، نويسنده , , Himisha Beltran، نويسنده , , Robert C. Onofrio، نويسنده , , et al، نويسنده ,
Abstract :
The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term “chromoplexy,” frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis.
