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Steely, Cody J; Russell, Kristi L; Feusier, Julie E; Qiao, Yi; Tavtigian, Sean V; Marth, Gabor; Jorde, Lynn B
Scientific reports, 06/2021, Letnik: 11, Številka: 1Journal Article
While mobile elements are largely inactive in healthy somatic tissues, increased activity has been found in cancer tissues, with significant variation among different cancer types. In addition to insertion events, mobile elements have also been found to mediate many structural variation events in the genome. Here, to better understand the timing and impact of mobile element insertions and associated structural variants in cancer, we examined their activity in longitudinal samples of four metastatic breast cancer patients. We identified 11 mobile element insertions or associated structural variants and found that the majority of these occurred early in tumor progression. Most of the variants impact intergenic regions; however, we identified a translocation interrupting MAP2K4 involving Alu elements and a deletion in YTHDF2 involving mobile elements that likely inactivate reported tumor suppressor genes. The high variant allele fraction of the translocation, the loss of the other copy of MAP2K4, the recurrent loss-of-function mutations found in this gene in other cancers, and the important function of MAP2K4 indicate that this translocation is potentially a driver mutation. Overall, using a unique longitudinal dataset, we find that most variants are likely passenger mutations in the four patients we examined, but some variants impact tumor progression.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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