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Cytogenomic Profile of Uterine Leiomyoma: In Vivo vs. In Vitro Comparison
We performed a comparative cytogenomic analysis of cultured and uncultured uterine leiomyoma (UL) samples. The experimental approach included karyotyping, aCGH, verification of the detected chromosomal abnormalities by metaphase and interphase FISH, MED12 mutation analysis and telomere measurement b...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698342/ https://www.ncbi.nlm.nih.gov/pubmed/34944592 http://dx.doi.org/10.3390/biomedicines9121777 |
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author | Koltsova, Alla S. Efimova, Olga A. Malysheva, Olga V. Osinovskaya, Natalia S. Liehr, Thomas Al-Rikabi, Ahmed Shved, Natalia Yu. Sultanov, Iskender Yu. Chiryaeva, Olga G. Yarmolinskaya, Maria I. Polenov, Nikolai I. Kunitsa, Vladislava V. Kakhiani, Maka I. Tral, Tatyana G. Tolibova, Gulrukhsor Kh. Bespalova, Olesya N. Kogan, Igor Yu. Glotov, Andrey S. Baranov, Vladislav S. Pendina, Anna A. |
author_facet | Koltsova, Alla S. Efimova, Olga A. Malysheva, Olga V. Osinovskaya, Natalia S. Liehr, Thomas Al-Rikabi, Ahmed Shved, Natalia Yu. Sultanov, Iskender Yu. Chiryaeva, Olga G. Yarmolinskaya, Maria I. Polenov, Nikolai I. Kunitsa, Vladislava V. Kakhiani, Maka I. Tral, Tatyana G. Tolibova, Gulrukhsor Kh. Bespalova, Olesya N. Kogan, Igor Yu. Glotov, Andrey S. Baranov, Vladislav S. Pendina, Anna A. |
author_sort | Koltsova, Alla S. |
collection | PubMed |
description | We performed a comparative cytogenomic analysis of cultured and uncultured uterine leiomyoma (UL) samples. The experimental approach included karyotyping, aCGH, verification of the detected chromosomal abnormalities by metaphase and interphase FISH, MED12 mutation analysis and telomere measurement by Q-FISH. An abnormal karyotype was detected in 12 out of 32 cultured UL samples. In five karyotypically abnormal ULs, MED12 mutations were found. The chromosomal abnormalities in ULs were present mostly by complex rearrangements, including chromothripsis. In both karyotypically normal and abnormal ULs, telomeres were ~40% shorter than in the corresponding myometrium, being possibly prerequisite to chromosomal rearrangements. The uncultured samples of six karyotypically abnormal ULs were checked for the detected chromosomal abnormalities through interphase FISH with individually designed DNA probe sets. All chromosomal abnormalities detected in cultured ULs were found in corresponding uncultured samples. In all tumors, clonal spectra were present by the karyotypically abnormal cell clone/clones which coexisted with karyotypically normal ones, suggesting that chromosomal abnormalities acted as drivers, rather than triggers, of the neoplastic process. In vitro propagation did not cause any changes in the spectrum of the cell clones, but altered their ratio compared to uncultured sample. The alterations were unique for every UL. Compared to its uncultured counterpart, the frequency of chromosomally abnormal cells in the cultured sample was higher in some ULs and lower in others. To summarize, ULs are characterized by both inter- and intratumor genetic heterogeneity. Regardless of its MED12 status, a tumor may be comprised of clones with and without chromosomal abnormalities. In contrast to the clonal spectrum, which is unique and constant for each UL, the clonal frequency demonstrates up or down shifts under in vitro conditions, most probably determined by the unequal ability of cells with different genetic aberrations to exist outside the body. |
format | Online Article Text |
id | pubmed-8698342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86983422021-12-24 Cytogenomic Profile of Uterine Leiomyoma: In Vivo vs. In Vitro Comparison Koltsova, Alla S. Efimova, Olga A. Malysheva, Olga V. Osinovskaya, Natalia S. Liehr, Thomas Al-Rikabi, Ahmed Shved, Natalia Yu. Sultanov, Iskender Yu. Chiryaeva, Olga G. Yarmolinskaya, Maria I. Polenov, Nikolai I. Kunitsa, Vladislava V. Kakhiani, Maka I. Tral, Tatyana G. Tolibova, Gulrukhsor Kh. Bespalova, Olesya N. Kogan, Igor Yu. Glotov, Andrey S. Baranov, Vladislav S. Pendina, Anna A. Biomedicines Article We performed a comparative cytogenomic analysis of cultured and uncultured uterine leiomyoma (UL) samples. The experimental approach included karyotyping, aCGH, verification of the detected chromosomal abnormalities by metaphase and interphase FISH, MED12 mutation analysis and telomere measurement by Q-FISH. An abnormal karyotype was detected in 12 out of 32 cultured UL samples. In five karyotypically abnormal ULs, MED12 mutations were found. The chromosomal abnormalities in ULs were present mostly by complex rearrangements, including chromothripsis. In both karyotypically normal and abnormal ULs, telomeres were ~40% shorter than in the corresponding myometrium, being possibly prerequisite to chromosomal rearrangements. The uncultured samples of six karyotypically abnormal ULs were checked for the detected chromosomal abnormalities through interphase FISH with individually designed DNA probe sets. All chromosomal abnormalities detected in cultured ULs were found in corresponding uncultured samples. In all tumors, clonal spectra were present by the karyotypically abnormal cell clone/clones which coexisted with karyotypically normal ones, suggesting that chromosomal abnormalities acted as drivers, rather than triggers, of the neoplastic process. In vitro propagation did not cause any changes in the spectrum of the cell clones, but altered their ratio compared to uncultured sample. The alterations were unique for every UL. Compared to its uncultured counterpart, the frequency of chromosomally abnormal cells in the cultured sample was higher in some ULs and lower in others. To summarize, ULs are characterized by both inter- and intratumor genetic heterogeneity. Regardless of its MED12 status, a tumor may be comprised of clones with and without chromosomal abnormalities. In contrast to the clonal spectrum, which is unique and constant for each UL, the clonal frequency demonstrates up or down shifts under in vitro conditions, most probably determined by the unequal ability of cells with different genetic aberrations to exist outside the body. MDPI 2021-11-26 /pmc/articles/PMC8698342/ /pubmed/34944592 http://dx.doi.org/10.3390/biomedicines9121777 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Koltsova, Alla S. Efimova, Olga A. Malysheva, Olga V. Osinovskaya, Natalia S. Liehr, Thomas Al-Rikabi, Ahmed Shved, Natalia Yu. Sultanov, Iskender Yu. Chiryaeva, Olga G. Yarmolinskaya, Maria I. Polenov, Nikolai I. Kunitsa, Vladislava V. Kakhiani, Maka I. Tral, Tatyana G. Tolibova, Gulrukhsor Kh. Bespalova, Olesya N. Kogan, Igor Yu. Glotov, Andrey S. Baranov, Vladislav S. Pendina, Anna A. Cytogenomic Profile of Uterine Leiomyoma: In Vivo vs. In Vitro Comparison |
title | Cytogenomic Profile of Uterine Leiomyoma: In Vivo vs. In Vitro Comparison |
title_full | Cytogenomic Profile of Uterine Leiomyoma: In Vivo vs. In Vitro Comparison |
title_fullStr | Cytogenomic Profile of Uterine Leiomyoma: In Vivo vs. In Vitro Comparison |
title_full_unstemmed | Cytogenomic Profile of Uterine Leiomyoma: In Vivo vs. In Vitro Comparison |
title_short | Cytogenomic Profile of Uterine Leiomyoma: In Vivo vs. In Vitro Comparison |
title_sort | cytogenomic profile of uterine leiomyoma: in vivo vs. in vitro comparison |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698342/ https://www.ncbi.nlm.nih.gov/pubmed/34944592 http://dx.doi.org/10.3390/biomedicines9121777 |
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