All y’all need to know ‘bout retroelements in cancer

Abstract

Genetic instability is one of the principal hallmarks and causative factors in cancer. Human transposable elements (TE) have been reported to cause human diseases, including several types of cancer through insertional mutagenesis of genes critical for preventing or driving malignant transformation. In addition to retrotransposition-associated mutagenesis, TEs have been found to contribute even more genomic rearrangements through non-allelic homologous recombination. TEs also have the potential to generate a wide range of mutations derivation of which is difficult to directly trace to mobile elements, including double-strand breaks that may trigger mutagenic genomic rearrangements. Genome-wide hypomethylation of TE promoters and significantly elevated TE expression in almost all human cancers often accompanied by the loss of critical DNA sensing and repair pathways suggests that the negative impact of mobile elements on genome stability should increase as human tumors evolve. The biological consequences of elevated retroelement expression, such as the rate of their amplification, in human cancers remain obscure, particularly, how this increase translates into disease-relevant mutations. This review is focused on the cellular mechanisms that control human TE-associated mutagenesis in cancer and summarizes the current understanding of TE contribution to genetic instability in human malignancies.

Extension of Saccharomyces paradoxus Chronological Lifespan by Retrotransposons in Certain Media Conditions Is Associated with Changes in Reactive Oxygen Species

“…Dispersed copies of retrotransposons that are subject to chromatin modifications and that initiate transcripts that can read through into neighboring genes may alter gene expression patterns (Slotkin and Martienssen 2007), which could affect cellular stress responses. Chimeric transcripts containing retrotransposon sequences and sequences of other genes are observed in human cells, including tumor cells, and can regulate gene expression (Belancio et al 2010;Cruickshanks et al 2013). Chromatin marks on mammalian short-interspersed nuclear element (SINE) retrotransposons can change in response to stress (Hunter et al 2012), and RNA from these elements can directly interact with RNA polymerase to influence gene expression in response to heat shock (Ponicsan et al 2010).…”

Domesticated transposable element gene products in human cancer

“…[8][9][10][11] The best characterized roles for TEs in tumorigenesis involve active mobilization or genomic rearrangement through recombination events. Although most TE sequences within the human genome have sustained mutations rendering them inactive, an estimated 80-100 elements retain the ability to transpose.…”

On the concept of biological function, junk DNA and the gospels of ENCODE and Grauret al.

“…A dramatic example of the problems associated with insertional oncogenic transformation is from the highly promising biomedical field of gene therapy using viral vectors, which has been devastated by high prevalence of cancer in treated patients [8][9][10][11][12]. It is relevant to mention also that insertional transformation has been one of the main and most effective approaches for identifying and mapping genes and regulatory elements implicated in cancer [13][14][15], which points to the tremendous selection pressure imposed by cancer-inducing insertion mutagenesis in multicellular organisms.…”