Mobile element insertions and associated structural variants in longitudinal breast cancer samples

Abstract 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 eve...

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Autores principales:	Cody J. Steely, Kristi L. Russell, Julie E. Feusier, Yi Qiao, Sean V. Tavtigian, Gabor Marth, Lynn B. Jorde
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6fa8c41e5cbf4b1ab6bff3501f6e8035
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spelling	oai:doaj.org-article:6fa8c41e5cbf4b1ab6bff3501f6e80352021-12-02T16:05:54ZMobile element insertions and associated structural variants in longitudinal breast cancer samples10.1038/s41598-021-92444-02045-2322https://doaj.org/article/6fa8c41e5cbf4b1ab6bff3501f6e80352021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92444-0https://doaj.org/toc/2045-2322Abstract 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.Cody J. SteelyKristi L. RussellJulie E. FeusierYi QiaoSean V. TavtigianGabor MarthLynn B. JordeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cody J. Steely Kristi L. Russell Julie E. Feusier Yi Qiao Sean V. Tavtigian Gabor Marth Lynn B. Jorde Mobile element insertions and associated structural variants in longitudinal breast cancer samples
description	Abstract 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.
format	article
author	Cody J. Steely Kristi L. Russell Julie E. Feusier Yi Qiao Sean V. Tavtigian Gabor Marth Lynn B. Jorde
author_facet	Cody J. Steely Kristi L. Russell Julie E. Feusier Yi Qiao Sean V. Tavtigian Gabor Marth Lynn B. Jorde
author_sort	Cody J. Steely
title	Mobile element insertions and associated structural variants in longitudinal breast cancer samples
title_short	Mobile element insertions and associated structural variants in longitudinal breast cancer samples
title_full	Mobile element insertions and associated structural variants in longitudinal breast cancer samples
title_fullStr	Mobile element insertions and associated structural variants in longitudinal breast cancer samples
title_full_unstemmed	Mobile element insertions and associated structural variants in longitudinal breast cancer samples
title_sort	mobile element insertions and associated structural variants in longitudinal breast cancer samples
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6fa8c41e5cbf4b1ab6bff3501f6e8035
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Mobile element insertions and associated structural variants in longitudinal breast cancer samples

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