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Massive LINE1 retrotransposon Invasion in Tuberous Sclerosis Astrocytomas

ABSTRACT: Somatic retrotranspositions of various mobile genetic elements take place in tumors, and L1 retroelements physiologically transpose in neural progenitor cells during neurogenesis. We sequenced whole genomes of the neural progenitor cell-derived subependymal giant cell astrocytomas that typically affect patients suffering from the neurodevelopmental disease Tuberous Sclerosis. Here we show an unprecedented increased L1 retrotransposition in these tumors, with tens of thousands new genomic insertions, that preferentially invade genes involved in neural activity, synaptic transmission and cancer. The prevalent insertions are short, nested in preexisting L1 repeats in the same orientation, trimmed in both the 5’ and 3’ ends, representing unorthodox retrotransposition”. Most somatic L1 inserts in the genomically stable astrocytomas are nested in preexisting L1 elements. This preferred nested integration may act as a “lightning rod” mechanism dampening the effects of massive retrotransposition. In contrast, the enhanced transposition found in genomically unstable breast tumors includes regions of high-density clustered insertion, transposminos. These clustered insertions are expected to be more detrimental, as many of them are non-nested and frequently invade genic and exonic sequences. Exaggerated L1 retrotransposition may be a common stochastic damaging pathway in neurological disorders and cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE56871 | GEO | 2016/12/31

SECONDARY ACCESSION(S): PRJNA244833

REPOSITORIES: GEO

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