We also find L1-mediated DSBs can generate diverse types of large-scale intrachromosomal rearrangements, including deletions and duplications. Interestingly, we find L1 caused a pericentric ring chromosome!

Similar to balanced translocations, we find that end joining between distal L1-mediated DSBs can generate dicentric or acentric chromosomes that result in complex rearrangements via breakage-fusion-bridge cycles or DNA fragmentation (chromothripsis).

For example, we show that L1-mediated DSBs from two distinct chromosomes can generate reciprocal balanced translocations (DNA copy number neutral), with one of the translocation junctions showing clear L1 TPRT evidence and the other lacking obvious evidence of L1 TPRT.

Here, we highlight the recombinogenic potential of DNA break ends of L1-mediated DSBs, with the DNA ends extended by TPRT leading to rearrangement junctions with L1 insertions and the reciprocal DNA ends leading to rearrangement junctions without evidence of L1 TPRT.

L1 retrotransposition occurs via target-primed reverse transcription (TPRT): L1 ORF2p nicks genomic DNA (3′-AA/TTTT-5′) to form a primer-template structure and then reverse transcribes the RNA to create L1 cDNA that is converted to double-stranded DNA as an insertion

L1 is the only active protein-coding transposon in humans: ORF1p (RNA binding protein) and ORF2p (endonuclease/reverse transcriptase).

My mentor Dr. Burns established L1 is derepressed in cancers, showing ORF1p detection in malignant tissues and somatic L1 copies in cancer genomes