Extensive somatic L1 retrotransposition in colorectal tumors

Solyom, Szilvia, Ewing, Adam D., Rahrmann, Eric P., Doucet, Tara, Nelson, Heather H., Burns, Michael B., Harris, Reuben S., Sigmon, David F., Casella, Alex, Erlanger, Bracha, Wheelan, Sarah, Upton, Kyle R., Shukla, Ruchi, Faulkner, Geoffrey J., Largaespada, David A. and Kazazian, Haig H. (2012) Extensive somatic L1 retrotransposition in colorectal tumors. Genome Research, 22 12: 2328-2338. doi:10.1101/gr.145235.112

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Author Solyom, Szilvia
Ewing, Adam D.
Rahrmann, Eric P.
Doucet, Tara
Nelson, Heather H.
Burns, Michael B.
Harris, Reuben S.
Sigmon, David F.
Casella, Alex
Erlanger, Bracha
Wheelan, Sarah
Upton, Kyle R.
Shukla, Ruchi
Faulkner, Geoffrey J.
Largaespada, David A.
Kazazian, Haig H.
Title Extensive somatic L1 retrotransposition in colorectal tumors
Journal name Genome Research   Check publisher's open access policy
ISSN 1088-9051
1549-5469
Publication date 2012-12
Sub-type Article (original research)
DOI 10.1101/gr.145235.112
Open Access Status File (Publisher version)
Volume 22
Issue 12
Start page 2328
End page 2338
Total pages 11
Place of publication Cold Spring Harbor, NY, United States
Publisher Cold Spring Harbor Laboratory Press
Collection year 2013
Language eng
Formatted abstract
L1 retrotransposons comprise 17% of the human genome and are its only autonomous mobile elements. Although L1-induced insertional mutagenesis causes Mendelian disease, their mutagenic load in cancer has been elusive. Using L1-targeted resequencing of 16 colorectal tumor and matched normal DNAs, we found that certain cancers were excessively mutagenized by human-specific L1s, while no verifiable insertions were present in normal tissues. We confirmed de novo L1 insertions in malignancy by both validating and sequencing 69/107 tumor-specific insertions and retrieving both 59 and 39 junctions for 35. In contrast to germline polymorphic L1s, all insertions were severely 59 truncated. Validated insertion numbers varied from up to 17 in some tumors to none in three others, and correlated with the age of the patients. Numerous genes with a role in tumorigenesis were targeted, including ODZ3, ROBO2, PTPRM, PCM1, and CDH11. Thus, somatic retrotransposition may play an etiologic role in colorectal cancer.
Keyword Cancer
Human Genomes
Processed Pseudogenes
Reverse Transcription
Sva Elements
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Biomedical Sciences Publications
 
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