Analyzing Somatic Genome Rearrangements in Human Cancers by Using Whole-Exome Sequencing

作者：Yang Lixing; Lee Mi Sook; Lu Hengyu; Oh Doo Yi; Kim Yeon Jeong; Park Donghyun; Park Gahee; Ren Xiaojia; Bristow Christopher A; Haseley Psalm S; Lee Soohyun; Pantazi Angeliki; Kucherlapati Raju; Park Woong Yang; Scott Kenneth L; Choi Yoon La^*; Park Peter J^*

来源：American Journal of Human Genetics, 2016, 98(5): 843-856.

DOI：10.1016/j.ajhg.2016.03.017

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 50 fusion partners of functional fusions are often housekeeping genes, whereas the 30 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 similar to 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.

• 出版日期2016-5-5