@article {701466, title = {Analyzing Somatic Genome Rearrangements in Human Cancers by Using Whole-Exome Sequencing.}, journal = {Am J Hum Genet}, volume = {98}, number = {5}, year = {2016}, month = {2016 May 5}, pages = {843-56}, abstract = { Although exome sequencing data are generated primarily to detect single-nucleotide variants and indels, they can also be used to identify a subset of genomic rearrangements whose breakpoints are located in or near exons. Using \>4,600 tumor and normal pairs across 15 cancer types, we identified over 9,000 high confidence somatic rearrangements, including a large number of gene fusions. We find that the 5{\textquoteright} fusion partners of functional fusions are often housekeeping genes, whereas the 3{\textquoteright} fusion partners are enriched in tyrosine kinases. We establish the oncogenic potential of ROR1-DNAJC6 and CEP85L-ROS1 fusions by showing that they can promote cell proliferation in\ vitro and tumor formation in\ vivo. Furthermore, we found that \~{}4\% of the samples have massively rearranged chromosomes, many of which are associated with upregulation of oncogenes such as ERBB2 and TERT. Although the sensitivity of detecting structural alterations from exomes is considerably lower than that from whole genomes, this approach will be fruitful for the multitude of exomes that have been and will be generated, both in cancer and in other diseases. }, issn = {1537-6605}, doi = {10.1016/j.ajhg.2016.03.017}, author = {Yang, Lixing* and Lee, Mi-Sook* and Lu, Hengyu* and Oh, Doo-Yi and Yeon Jeong Kim and Donghyun Park and Park, Gahee and Ren, Xiaojia and Bristow, Christopher A and Haseley, Psalm S and Lee, Soohyun and Pantazi, Angeliki and Kucherlapati, Raju and Park, Woong-Yang and Scott, Kenneth L** and Choi, Yoon-La** and Park, Peter J**} }