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The three-dimensional organization of telomeres in the nucleus of mammalian cells.

Chuang TC, Moshir S, Garini Y, Chuang AY, Young IT, Vermolen B, van den Doel R, Mougey V, Perrin M, Braun M, Kerr PD, Fest T, Boukamp P, Mai S - BMC Biol. (2004)

Bottom Line: In tumor cells, the 3D telomere organization is distorted and aggregates are formed.The results emphasize a non-random and dynamic 3D nuclear telomeric organization and its importance to genomic stability.Based on our findings, it appears possible to examine telomeric aggregates suggestive of genomic instability in individual interphase nuclei and tissues without the need to examine metaphases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, 675 McDermot Avenue, Winnipeg, MB, R3E 0V9, Canada. tcychuang@hotmail.com

ABSTRACT

Background: The observation of multiple genetic markers in situ by optical microscopy and their relevance to the study of three-dimensional (3D) chromosomal organization in the nucleus have been greatly developed in the last decade. These methods are important in cancer research because cancer is characterized by multiple alterations that affect the modulation of gene expression and the stability of the genome. It is, therefore, essential to analyze the 3D genome organization of the interphase nucleus in both normal and cancer cells.

Results: We describe a novel approach to study the distribution of all telomeres inside the nucleus of mammalian cells throughout the cell cycle. It is based on 3D telomere fluorescence in situ hybridization followed by quantitative analysis that determines the telomeres' distribution in the nucleus throughout the cell cycle. This method enables us to determine, for the first time, that telomere organization is cell-cycle dependent, with assembly of telomeres into a telomeric disk in the G2 phase. In tumor cells, the 3D telomere organization is distorted and aggregates are formed.

Conclusions: The results emphasize a non-random and dynamic 3D nuclear telomeric organization and its importance to genomic stability. Based on our findings, it appears possible to examine telomeric aggregates suggestive of genomic instability in individual interphase nuclei and tissues without the need to examine metaphases. Such new avenues of monitoring genomic instability could potentially impact on cancer biology, genetics, diagnostic innovations and surveillance of treatment response in medicine.

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Normal: A normal blood cell; RAJI: A Burkitt lymphoma cell line; PCT: A primary mouse plasmacytoma cell; HNSCC: A primary human head and neck squamous cell carcinoma (stage IV). The distribution of telomeres in cancer cells compared with a normal cell. Images are shown as explained in Fig. 5. Aggregates of telomeres are formed and the telomere disk that appears in the G2 phase is distorted.
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Figure 7: Normal: A normal blood cell; RAJI: A Burkitt lymphoma cell line; PCT: A primary mouse plasmacytoma cell; HNSCC: A primary human head and neck squamous cell carcinoma (stage IV). The distribution of telomeres in cancer cells compared with a normal cell. Images are shown as explained in Fig. 5. Aggregates of telomeres are formed and the telomere disk that appears in the G2 phase is distorted.

Mentions: We have continued to observe the distribution of telomeres in cancer cells. Typical 3D images constructed from normal nuclei and from a Burkitt lymphoma cell line (Raji), as well as from primary mouse plasmacytoma (PCT) and primary human head and neck squamous cell carcinoma (HNSCC) stage IV (Fig. 7), show that telomeres form aggregates and thus a partially altered telomeric disk. Such telomeric aggregates are characterized by both a larger volume and larger integrated intensity than their normal non-overlapping and non-aggregated counterparts. They are not observed in normal cells. Similar results for altered telomeric organization have also been found in human neuroblastoma and colon carcinoma tumor cell lines.


The three-dimensional organization of telomeres in the nucleus of mammalian cells.

Chuang TC, Moshir S, Garini Y, Chuang AY, Young IT, Vermolen B, van den Doel R, Mougey V, Perrin M, Braun M, Kerr PD, Fest T, Boukamp P, Mai S - BMC Biol. (2004)

Normal: A normal blood cell; RAJI: A Burkitt lymphoma cell line; PCT: A primary mouse plasmacytoma cell; HNSCC: A primary human head and neck squamous cell carcinoma (stage IV). The distribution of telomeres in cancer cells compared with a normal cell. Images are shown as explained in Fig. 5. Aggregates of telomeres are formed and the telomere disk that appears in the G2 phase is distorted.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC425602&req=5

Figure 7: Normal: A normal blood cell; RAJI: A Burkitt lymphoma cell line; PCT: A primary mouse plasmacytoma cell; HNSCC: A primary human head and neck squamous cell carcinoma (stage IV). The distribution of telomeres in cancer cells compared with a normal cell. Images are shown as explained in Fig. 5. Aggregates of telomeres are formed and the telomere disk that appears in the G2 phase is distorted.
Mentions: We have continued to observe the distribution of telomeres in cancer cells. Typical 3D images constructed from normal nuclei and from a Burkitt lymphoma cell line (Raji), as well as from primary mouse plasmacytoma (PCT) and primary human head and neck squamous cell carcinoma (HNSCC) stage IV (Fig. 7), show that telomeres form aggregates and thus a partially altered telomeric disk. Such telomeric aggregates are characterized by both a larger volume and larger integrated intensity than their normal non-overlapping and non-aggregated counterparts. They are not observed in normal cells. Similar results for altered telomeric organization have also been found in human neuroblastoma and colon carcinoma tumor cell lines.

Bottom Line: In tumor cells, the 3D telomere organization is distorted and aggregates are formed.The results emphasize a non-random and dynamic 3D nuclear telomeric organization and its importance to genomic stability.Based on our findings, it appears possible to examine telomeric aggregates suggestive of genomic instability in individual interphase nuclei and tissues without the need to examine metaphases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, 675 McDermot Avenue, Winnipeg, MB, R3E 0V9, Canada. tcychuang@hotmail.com

ABSTRACT

Background: The observation of multiple genetic markers in situ by optical microscopy and their relevance to the study of three-dimensional (3D) chromosomal organization in the nucleus have been greatly developed in the last decade. These methods are important in cancer research because cancer is characterized by multiple alterations that affect the modulation of gene expression and the stability of the genome. It is, therefore, essential to analyze the 3D genome organization of the interphase nucleus in both normal and cancer cells.

Results: We describe a novel approach to study the distribution of all telomeres inside the nucleus of mammalian cells throughout the cell cycle. It is based on 3D telomere fluorescence in situ hybridization followed by quantitative analysis that determines the telomeres' distribution in the nucleus throughout the cell cycle. This method enables us to determine, for the first time, that telomere organization is cell-cycle dependent, with assembly of telomeres into a telomeric disk in the G2 phase. In tumor cells, the 3D telomere organization is distorted and aggregates are formed.

Conclusions: The results emphasize a non-random and dynamic 3D nuclear telomeric organization and its importance to genomic stability. Based on our findings, it appears possible to examine telomeric aggregates suggestive of genomic instability in individual interphase nuclei and tissues without the need to examine metaphases. Such new avenues of monitoring genomic instability could potentially impact on cancer biology, genetics, diagnostic innovations and surveillance of treatment response in medicine.

Show MeSH
Related in: MedlinePlus