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Open AccessArticle

Somatic Mutations in miRNA Genes in Lung Cancer—Potential Functional Consequences of Non-Coding Sequence Variants

1
Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Poland
2
Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland
3
The F. Lukaszczyk Oncology Center, Department of Molecular Oncology and Genetics, 85-796 Bydgoszcz, Poland
4
The Ludwik Rydygier Collegium Medicum, Department of Thoracic Surgery and Tumours, Nicolaus Copernicus University, 85-796 Bydgoszcz, Poland
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(6), 793; https://doi.org/10.3390/cancers11060793
Received: 16 April 2019 / Revised: 6 June 2019 / Accepted: 6 June 2019 / Published: 8 June 2019
A growing body of evidence indicates that miRNAs may either drive or suppress oncogenesis. However, little is known about somatic mutations in miRNA genes. To determine the frequency and potential consequences of miRNA gene mutations, we analyzed whole exome sequencing datasets of 569 lung adenocarcinoma (LUAD) and 597 lung squamous cell carcinoma (LUSC) samples generated in The Cancer Genome Atlas (TCGA) project. Altogether, we identified 1091 somatic sequence variants affecting 522 different miRNA genes and showed that half of all cancers had at least one such somatic variant/mutation. These sequence variants occurred in most crucial parts of miRNA precursors, including mature miRNA and seed sequences. Due to our findings, we hypothesize that seed mutations may affect miRNA:target interactions, drastically changing the pool of predicted targets. Mutations may also affect miRNA biogenesis by changing the structure of miRNA precursors, DROSHA and DICER cleavage sites, and regulatory sequence/structure motifs. We identified 10 significantly overmutated hotspot miRNA genes, including the miR-379 gene in LUAD enriched in mutations in the mature miRNA and regulatory sequences. The occurrence of mutations in the hotspot miRNA genes was also shown experimentally. We present a comprehensive analysis of somatic variants in miRNA genes and show that some of these genes are mutational hotspots, suggesting their potential role in cancer. View Full-Text
Keywords: miRNA; somatic mutations; lung cancer; TCGA; non-coding miRNA; somatic mutations; lung cancer; TCGA; non-coding
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Galka-Marciniak, P.; Urbanek-Trzeciak, M.O.; Nawrocka, P.M.; Dutkiewicz, A.; Giefing, M.; Lewandowska, M.A.; Kozlowski, P. Somatic Mutations in miRNA Genes in Lung Cancer—Potential Functional Consequences of Non-Coding Sequence Variants. Cancers 2019, 11, 793.

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