RT Journal
A1 Solyom, Szilvia
A1 Ewing, Adam D.
A1 Rahrmann, Eric P.
A1 Doucet, Tara
A1 Nelson, Heather H.
A1 Burns, Michael B.
A1 Harris, Reuben S.
A1 Sigmon, David F.
A1 Casella, Alex
A1 Erlanger, Bracha
A1 Wheelan, Sarah
A1 Upton, Kyle R.
A1 Shukla, Ruchi
A1 Faulkner, Geoffrey J.
A1 Largaespada, David A.
A1 Kazazian, Haig H.
T1 Extensive somatic L1 retrotransposition in colorectal tumors
JF Genome Research 
JO Genome Research 
YR 2012 
FD December 01 
VO 22 
IS 12 
SP 2328 
OP 2338 
DO 10.1101/gr.145235.112 
UL http://genome.cshlp.org/content/22/12/2328.abstract 
AB 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 5′ and 3′ junctions for 35. In contrast to germline polymorphic L1s, all insertions were severely 5′ 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.