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Characterization of MED12, HMGA2, and FH alterations reveals molecular variability in uterine smooth muscle tumors
Uterine smooth muscle tumors range from benign leiomyomas to malignant leiomyosarcomas. Based on numerous molecular studies, leiomyomas and leiomyosarcomas mostly lack shared mutations and the majority of tumors are believed to develop through distinct mechanisms. To further characterize the molecul...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5463371/ https://www.ncbi.nlm.nih.gov/pubmed/28592321 http://dx.doi.org/10.1186/s12943-017-0672-1 |
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author | Mäkinen, Netta Kämpjärvi, Kati Frizzell, Norma Bützow, Ralf Vahteristo, Pia |
author_facet | Mäkinen, Netta Kämpjärvi, Kati Frizzell, Norma Bützow, Ralf Vahteristo, Pia |
author_sort | Mäkinen, Netta |
collection | PubMed |
description | Uterine smooth muscle tumors range from benign leiomyomas to malignant leiomyosarcomas. Based on numerous molecular studies, leiomyomas and leiomyosarcomas mostly lack shared mutations and the majority of tumors are believed to develop through distinct mechanisms. To further characterize the molecular variability among uterine smooth muscle tumors, and simultaneously insinuate their potential malignant progression, we examined the frequency of known genetic leiomyoma driver alterations (MED12 mutations, HMGA2 overexpression, biallelic FH inactivation) in 65 conventional leiomyomas, 94 histopathological leiomyoma variants (18 leiomyomas with bizarre nuclei, 22 cellular, 29 highly cellular, and 25 mitotically active leiomyomas), and 51 leiomyosarcomas. Of the 210 tumors analyzed, 107 had mutations in one of the three driver genes. No tumor had more than one mutation confirming that all alterations are mutually exclusive. MED12 mutations were the most common alterations in conventional and mitotically active leiomyomas and leiomyosarcomas, while leiomyomas with bizarre nuclei were most often FH deficient and cellular tumors showed frequent HMGA2 overexpression. Highly cellular leiomyomas displayed the least amount of alterations leaving the majority of tumors with no known driver aberration. Our results indicate that based on the molecular background, histopathological leiomyoma subtypes do not only differ from conventional leiomyomas, but also from each other. The presence of leiomyoma driver alterations in nearly one third of leiomyosarcomas suggests that some tumors arise through leiomyoma precursor lesion or that these mutations provide growth advantage also to highly aggressive cancers. It is clinically relevant to understand the molecular background of various smooth muscle tumor subtypes, as it may lead to improved diagnosis and personalized treatments in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-017-0672-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5463371 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-54633712017-06-08 Characterization of MED12, HMGA2, and FH alterations reveals molecular variability in uterine smooth muscle tumors Mäkinen, Netta Kämpjärvi, Kati Frizzell, Norma Bützow, Ralf Vahteristo, Pia Mol Cancer Letter to the Editor Uterine smooth muscle tumors range from benign leiomyomas to malignant leiomyosarcomas. Based on numerous molecular studies, leiomyomas and leiomyosarcomas mostly lack shared mutations and the majority of tumors are believed to develop through distinct mechanisms. To further characterize the molecular variability among uterine smooth muscle tumors, and simultaneously insinuate their potential malignant progression, we examined the frequency of known genetic leiomyoma driver alterations (MED12 mutations, HMGA2 overexpression, biallelic FH inactivation) in 65 conventional leiomyomas, 94 histopathological leiomyoma variants (18 leiomyomas with bizarre nuclei, 22 cellular, 29 highly cellular, and 25 mitotically active leiomyomas), and 51 leiomyosarcomas. Of the 210 tumors analyzed, 107 had mutations in one of the three driver genes. No tumor had more than one mutation confirming that all alterations are mutually exclusive. MED12 mutations were the most common alterations in conventional and mitotically active leiomyomas and leiomyosarcomas, while leiomyomas with bizarre nuclei were most often FH deficient and cellular tumors showed frequent HMGA2 overexpression. Highly cellular leiomyomas displayed the least amount of alterations leaving the majority of tumors with no known driver aberration. Our results indicate that based on the molecular background, histopathological leiomyoma subtypes do not only differ from conventional leiomyomas, but also from each other. The presence of leiomyoma driver alterations in nearly one third of leiomyosarcomas suggests that some tumors arise through leiomyoma precursor lesion or that these mutations provide growth advantage also to highly aggressive cancers. It is clinically relevant to understand the molecular background of various smooth muscle tumor subtypes, as it may lead to improved diagnosis and personalized treatments in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-017-0672-1) contains supplementary material, which is available to authorized users. BioMed Central 2017-06-07 /pmc/articles/PMC5463371/ /pubmed/28592321 http://dx.doi.org/10.1186/s12943-017-0672-1 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Letter to the Editor Mäkinen, Netta Kämpjärvi, Kati Frizzell, Norma Bützow, Ralf Vahteristo, Pia Characterization of MED12, HMGA2, and FH alterations reveals molecular variability in uterine smooth muscle tumors |
title | Characterization of MED12, HMGA2, and FH alterations reveals molecular variability in uterine smooth muscle tumors |
title_full | Characterization of MED12, HMGA2, and FH alterations reveals molecular variability in uterine smooth muscle tumors |
title_fullStr | Characterization of MED12, HMGA2, and FH alterations reveals molecular variability in uterine smooth muscle tumors |
title_full_unstemmed | Characterization of MED12, HMGA2, and FH alterations reveals molecular variability in uterine smooth muscle tumors |
title_short | Characterization of MED12, HMGA2, and FH alterations reveals molecular variability in uterine smooth muscle tumors |
title_sort | characterization of med12, hmga2, and fh alterations reveals molecular variability in uterine smooth muscle tumors |
topic | Letter to the Editor |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5463371/ https://www.ncbi.nlm.nih.gov/pubmed/28592321 http://dx.doi.org/10.1186/s12943-017-0672-1 |
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