A hot L1 retrotransposon evades somatic repression and initiates human colorectal cancerReport as inadecuate




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Journal Title:

Genome Research

Volume:

Volume 26, Number 6

Publisher:

Cold Spring Harbor Laboratory Press | 2016-06-01, Pages 745-755

Type of Work:

Article | Final Publisher PDF

Abstract: Although human LINE-1 L1 elements are actively mobilized in many cancers, a role for somatic L1 retrotransposition in tumor initiation has not been conclusively demonstrated. Here, we identify a novel somatic L1 insertion in the APC tumor suppressor gene that provided us with a unique opportunity to determine whether such insertions can actually initiate colorectal cancer CRC, and if so, how this might occur. Our data support a model whereby a hot L1 source element on Chromosome 17 of the patient's genome evaded somatic repression in normal colon tissues and thereby initiated CRC by mutating the APC gene. This insertion worked together with a point mutation in the second APC allele to initiate tumor-igenesis through the classic two-hit CRC pathway. We also show that L1 source profiles vary considerably depending on the ancestry of an individual, and that population-specific hot L1 elements represent a novel form of cancer risk.

Subjects: Biology, Genetics - Biology, Microbiology - Health Sciences, Oncology - Research Funding: This work was funded by the following NIH grants: National Cancer Institute NCI grant T32 CA154274 E.C.S., National Institute of Diabetes and Digestive and Kidney Diseases grant T32 DK067872 N.T.C., NCI grant R01 CA077337 P.M.V., NCI grant R01 CA166661 S.E.D., and National Human Genome Research Institute grant R01 HG002898 S.E.D



Keywords: Science and Technology - Life Sciences and Biomedicine - Biochemistry and Molecular Biology - Biotechnology and Applied Microbiology - Genetics and Heredity - HUMAN GENOMES - APC GENE - CELLS - EVOLUTION - SEQUENCE - TRANSCRIPTION - MOSAICISM - MUTATIONS -



Author: Emma C. Scott, Eugene J. Gardner, Ashiq Masood, Nelson T. Chuang, Paula Vertino, Scott E. Devine,

Source: https://open.library.emory.edu/



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