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Telomere Shortening in Hematological Malignancies with Tetraploidization—A Mechanism for Chromosomal Instability?

Aneuploidy, the presence of an abnormal number of chromosomes in a cell, is one of the most obvious differences between normal and cancer cells. There is, however, debate on how aneuploid cells arise and whether or not they are a cause or a consequence of tumorigenesis. Further, it is important to d...

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Autor principal: Kjeldsen, Eigil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742813/
https://www.ncbi.nlm.nih.gov/pubmed/29189717
http://dx.doi.org/10.3390/cancers9120165
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author Kjeldsen, Eigil
author_facet Kjeldsen, Eigil
author_sort Kjeldsen, Eigil
collection PubMed
description Aneuploidy, the presence of an abnormal number of chromosomes in a cell, is one of the most obvious differences between normal and cancer cells. There is, however, debate on how aneuploid cells arise and whether or not they are a cause or a consequence of tumorigenesis. Further, it is important to distinguish aneuploidy (the “state” of the karyotype) from chromosomal instability (CIN; the “rate” of karyotypic change). Although CIN leads to aneuploidy, not all aneuploid cells exhibit CIN. One proposed route to aneuploid cells is through an unstable tetraploid intermediate because tetraploidy promotes chromosomal aberrations and tumorigenesis. Tetraploidy or near-tetraploidy (T/NT) (81–103 chromosomes) karyotypes with or without additional structural abnormalities have been reported in acute leukemia, T-cell and B-cell lymphomas, and solid tumors. In solid tumors it has been shown that tetraploidization can occur in response to loss of telomere protection in the early stages of tumorigenesis in colon cancer, Barrett’s esophagus, and breast and cervical cancers. In hematological malignancies T/NT karyotypes are rare and the role of telomere dysfunction for the induction of tetraploidization is less well characterized. To further our understanding of possible telomere dysfunction as a mechanism for tetrapolydization in hematological cancers we here characterized the chromosomal complement and measured the telomere content by interphase nuclei quantitative fluorescence in situ hybridization (iQFISH) in seven hematological cancer patients with T/NT karyotypes, and after cytogenetic remission. The patients were identified after a search in our local cytogenetic registry in the 5-year period between June 2012 and May 2017 among more than 12,000 analyzed adult patients in this period. One advantage of measuring telomere content by iQFISH is that it is a single-cell analysis so that the telomere content can be distinguished between normal karyotype cells and cells with T/NT karyotypes. We find that the telomeres are particularly short in cells with T/NT karyotypes as compared with normal cells, and in T/NT karyotypes harboring additional chromosomal aberrations as well. These findings suggest that telomere dysfunction in hematological malignancies may be a mechanism for tetraploidization and CIN.
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spelling pubmed-57428132017-12-29 Telomere Shortening in Hematological Malignancies with Tetraploidization—A Mechanism for Chromosomal Instability? Kjeldsen, Eigil Cancers (Basel) Article Aneuploidy, the presence of an abnormal number of chromosomes in a cell, is one of the most obvious differences between normal and cancer cells. There is, however, debate on how aneuploid cells arise and whether or not they are a cause or a consequence of tumorigenesis. Further, it is important to distinguish aneuploidy (the “state” of the karyotype) from chromosomal instability (CIN; the “rate” of karyotypic change). Although CIN leads to aneuploidy, not all aneuploid cells exhibit CIN. One proposed route to aneuploid cells is through an unstable tetraploid intermediate because tetraploidy promotes chromosomal aberrations and tumorigenesis. Tetraploidy or near-tetraploidy (T/NT) (81–103 chromosomes) karyotypes with or without additional structural abnormalities have been reported in acute leukemia, T-cell and B-cell lymphomas, and solid tumors. In solid tumors it has been shown that tetraploidization can occur in response to loss of telomere protection in the early stages of tumorigenesis in colon cancer, Barrett’s esophagus, and breast and cervical cancers. In hematological malignancies T/NT karyotypes are rare and the role of telomere dysfunction for the induction of tetraploidization is less well characterized. To further our understanding of possible telomere dysfunction as a mechanism for tetrapolydization in hematological cancers we here characterized the chromosomal complement and measured the telomere content by interphase nuclei quantitative fluorescence in situ hybridization (iQFISH) in seven hematological cancer patients with T/NT karyotypes, and after cytogenetic remission. The patients were identified after a search in our local cytogenetic registry in the 5-year period between June 2012 and May 2017 among more than 12,000 analyzed adult patients in this period. One advantage of measuring telomere content by iQFISH is that it is a single-cell analysis so that the telomere content can be distinguished between normal karyotype cells and cells with T/NT karyotypes. We find that the telomeres are particularly short in cells with T/NT karyotypes as compared with normal cells, and in T/NT karyotypes harboring additional chromosomal aberrations as well. These findings suggest that telomere dysfunction in hematological malignancies may be a mechanism for tetraploidization and CIN. MDPI 2017-11-30 /pmc/articles/PMC5742813/ /pubmed/29189717 http://dx.doi.org/10.3390/cancers9120165 Text en © 2017 by the author. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kjeldsen, Eigil
Telomere Shortening in Hematological Malignancies with Tetraploidization—A Mechanism for Chromosomal Instability?
title Telomere Shortening in Hematological Malignancies with Tetraploidization—A Mechanism for Chromosomal Instability?
title_full Telomere Shortening in Hematological Malignancies with Tetraploidization—A Mechanism for Chromosomal Instability?
title_fullStr Telomere Shortening in Hematological Malignancies with Tetraploidization—A Mechanism for Chromosomal Instability?
title_full_unstemmed Telomere Shortening in Hematological Malignancies with Tetraploidization—A Mechanism for Chromosomal Instability?
title_short Telomere Shortening in Hematological Malignancies with Tetraploidization—A Mechanism for Chromosomal Instability?
title_sort telomere shortening in hematological malignancies with tetraploidization—a mechanism for chromosomal instability?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742813/
https://www.ncbi.nlm.nih.gov/pubmed/29189717
http://dx.doi.org/10.3390/cancers9120165
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