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

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 adenocarc...
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Autor*in:	Paulina Galka-Marciniak [verfasserIn] Martyna Olga Urbanek-Trzeciak [verfasserIn] Paulina Maria Nawrocka [verfasserIn] Agata Dutkiewicz [verfasserIn] Maciej Giefing [verfasserIn] Marzena Anna Lewandowska [verfasserIn] Piotr Kozlowski [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	miRNA somatic mutations lung cancer TCGA non-coding

Übergeordnetes Werk:	In: Cancers - MDPI AG, 2010, 11(2019), 6, p 793
Übergeordnetes Werk:	volume:11 ; year:2019 ; number:6, p 793

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cancers11060793

Katalog-ID:	DOAJ019269293

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allfieldsSound	10.3390/cancers11060793 doi (DE-627)DOAJ019269293 (DE-599)DOAJ3e619583b8184496b6326f41b0c9a651 DE-627 ger DE-627 rakwb eng RC254-282 Paulina Galka-Marciniak verfasserin aut Somatic Mutations in miRNA Genes in Lung Cancer—Potential Functional Consequences of Non-Coding Sequence Variants 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. miRNA somatic mutations lung cancer TCGA non-coding Neoplasms. Tumors. Oncology. Including cancer and carcinogens Martyna Olga Urbanek-Trzeciak verfasserin aut Paulina Maria Nawrocka verfasserin aut Agata Dutkiewicz verfasserin aut Maciej Giefing verfasserin aut Marzena Anna Lewandowska verfasserin aut Piotr Kozlowski verfasserin aut In Cancers MDPI AG, 2010 11(2019), 6, p 793 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:11 year:2019 number:6, p 793 https://doi.org/10.3390/cancers11060793 kostenfrei https://doaj.org/article/3e619583b8184496b6326f41b0c9a651 kostenfrei https://www.mdpi.com/2072-6694/11/6/793 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2019 6, p 793
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authorswithroles_txt_mv	Paulina Galka-Marciniak @@aut@@ Martyna Olga Urbanek-Trzeciak @@aut@@ Paulina Maria Nawrocka @@aut@@ Agata Dutkiewicz @@aut@@ Maciej Giefing @@aut@@ Marzena Anna Lewandowska @@aut@@ Piotr Kozlowski @@aut@@
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callnumber-first	R - Medicine
author	Paulina Galka-Marciniak
spellingShingle	Paulina Galka-Marciniak misc RC254-282 misc miRNA misc somatic mutations misc lung cancer misc TCGA misc non-coding misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Somatic Mutations in miRNA Genes in Lung Cancer—Potential Functional Consequences of Non-Coding Sequence Variants
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topic_title	RC254-282 Somatic Mutations in miRNA Genes in Lung Cancer—Potential Functional Consequences of Non-Coding Sequence Variants miRNA somatic mutations lung cancer TCGA non-coding
topic	misc RC254-282 misc miRNA misc somatic mutations misc lung cancer misc TCGA misc non-coding misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc miRNA misc somatic mutations misc lung cancer misc TCGA misc non-coding misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Somatic Mutations in miRNA Genes in Lung Cancer—Potential Functional Consequences of Non-Coding Sequence Variants
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title_full	Somatic Mutations in miRNA Genes in Lung Cancer—Potential Functional Consequences of Non-Coding Sequence Variants
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title_sort	somatic mutations in mirna genes in lung cancer—potential functional consequences of non-coding sequence variants
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title_auth	Somatic Mutations in miRNA Genes in Lung Cancer—Potential Functional Consequences of Non-Coding Sequence Variants
abstract	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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	Somatic Mutations in miRNA Genes in Lung Cancer—Potential Functional Consequences of Non-Coding Sequence Variants
url	https://doi.org/10.3390/cancers11060793 https://doaj.org/article/3e619583b8184496b6326f41b0c9a651 https://www.mdpi.com/2072-6694/11/6/793 https://doaj.org/toc/2072-6694
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up_date	2024-07-03T22:41:57.168Z
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Somatic Mutations in miRNA Genes in Lung Cancer—Potential Functional Consequences of Non-Coding Sequence Variants

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