Changes in Nuclear Orientation Patterns of Chromosome 11 during Mouse Plasmacytoma Development

Schmälter, Ann-Kristin; Righolt, Christiaan H.; Kuzyk, Alexandra; Mai, Sabine

doi:10.1016/j.tranon.2015.09.001

Cited by 4 publications

(4 citation statements)

References 34 publications

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“…The nuclear architecture of cancer cell nuclei is unique. These nuclei undergo dynamic structural aberrations that include changes in their 3D organization of telomeres, chromosomes and chromosome orientation (Mai, ; Gadji et al, ; Righolt et al, ; Martin et al, ; Schmälter et al, ). This study demonstrates that the tumor cell‐specific 3D nuclear telomere organization is sensitive to XPO1 inhibition.…”

Section: Discussionmentioning

confidence: 99%

XPO1 Inhibition Preferentially Disrupts the 3D Nuclear Organization of Telomeres in Tumor Cells

Taylor-Kashton

Lichtensztejn

Baloglu

et al. 2016

Journal Cellular Physiology

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Previous work has shown that the three‐dimensional (3D) nuclear organization of telomeres is altered in cancer cells and the degree of alterations coincides with aggressiveness of disease. Nuclear pores are essential for spatial genome organization and gene regulation and XPO1 (exportin 1/CRM1) is the key nuclear export protein. The Selective Inhibitor of Nuclear Export (SINE) compounds developed by Karyopharm Therapeutics (KPT‐185, KPT‐330/selinexor, and KPT‐8602) inhibit XPO1 nuclear export function. In this study, we investigated whether XPO1 inhibition has downstream effects on the 3D nuclear organization of the genome. This was assessed by measuring the 3D telomeric architecture of normal and tumor cells in vitro and ex vivo. Our data demonstrate for the first time a rapid and preferential disruption of the 3D nuclear organization of telomeres in tumor cell lines and in primary cells ex vivo derived from treatment‐naïve newly diagnosed multiple myeloma patients. Normal primary cells in culture as well as healthy lymphocyte control cells from the same patients were minimally affected. Using both lymphoid and non‐lymphoid tumor cell lines, we found that the downstream effects on the 3D nuclear telomere structure are independent of tumor type. We conclude that the 3D nuclear organization of telomeres is a sensitive indicator of cellular response when treated with XPO1 inhibitors. J. Cell. Physiol. 231: 2711–2719, 2016. © 2016 The Authors. Journal of Cellular Physiology published by Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

XPO1 Inhibition Preferentially Disrupts the 3D Nuclear Organization of Telomeres in Tumor Cells

Taylor-Kashton

Lichtensztejn

Baloglu

et al. 2016

Journal Cellular Physiology

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“…Not much is known about the chromosomal orientation in normal and cancer cells. Multicolor‐banding approaches enabled a study of chromosome 11 orientation in normal mouse lymphocytes and in mouse plasmacytoma, compared to control cells . Normal mouse lymphocytes showed three common patterns of orientation, whereas significant differences in the orientation patterns of chromosome 11 were seen between plasmacytoma and control cells of the same mouse strain.…”

Section: The 3d Nucleus In Cancer Cells: Where We Are Today and Wherementioning

confidence: 99%

“…Schmälter et al studied mouse chromosome 11 in lymphocytes of [T38HxBALB/c]N mice with a reciprocal translocation between chromosome X and 11 (T38HT(X;11)) exhibiting a long chromosome T(11;X) and a short chromosome T(X;11) and in fast‐onset plasmacytomas (PCTs) induced in the same strain. They determined the 3D orientation of chromosome 11 using a mouse chromosome 11 specific multicolor banding probe.…”

Section: The 3d Nucleus In Cancer Cells: Where We Are Today and Wherementioning

confidence: 99%

The three‐dimensional cancer nucleus

Mai

2019

Genes Chromosomes & Cancer

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Research into the three‐dimensional (3D) organization of the cancer cell genome started over 100 years ago. We follow an exciting avenue of research in this field, from Hansemann's early observations of aberrant mitoses and nuclei in cancer cells in the late 19th century to Boveri's theory of the cancer cell in the early 20th century, to current views of nuclear organization and its changes in cancer. Molecular and imaging methods go hand in hand with providing us with a better understanding of the spatial nature of the cancer cell genome. This has led to the concept that the structural order of the nucleus can be used as cancer cell biomarker.

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“…Recent quantitative measurements of the three-dimensional (3D) genome structure of normal vs. tumor cell nuclei have indicated that these differences lie in the way the genome is organized. Using centromeres, telomeres, chromosomes, and DNA as tools to measure the 3D organization order, distinct changes can be identified and quantitated (RIGHOLT et al, 2014;SCHMÄLTER et al, 2015;VERMOLEN et al, 2005;YU et al, 2019). These studies have shown that the genome structure can serve as an architectural biomarker of cancer stage and aggressiveness (BABU;FULLWOOD, 2015;GADJI et al, 2010;RANGEL-POZZO et al, 2021a).…”

Section: Genomic Instabilitymentioning

confidence: 99%

3D nuclear architecture distinguishes thyroid neoplastic histotypes

Pozzo

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Molecular markers can be diagnostic tools to support pathological analysis in thyroid neoplasms. However, because the same markers can be observed in some benign thyroid lesions, additional approaches are necessary to differentiate thyroid tumour subtypes, prevent overtreatment and tailor specific clinical management. This applies particularly to the recently described variant of thyroid cancer referred to as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This variant has an estimated prevalence of 4.4% to 9.1% of all papillary thyroid carcinomas worldwide. We studied 60 thyroid lesions: 20 classical papillary thyroid carcinoma (CPTC), 20 follicular variants of PTC (FVPTC) and 20 NIFTP. We examined morphological and molecular features to identify parameters that can differentiate NIFTP from the other PTC subtypes.When blindly investigating the nuclear architecture of thyroid neoplasms, we observed that NIFTP has significantly longer telomeres than CPTC and FVPTC. Super-resolved 3Dstructured illumination microscopy demonstrated that NIFTP is heterogeneous and that its nuclei contain more densely packed DNA and smaller interchromatin spaces than CPTC and FVPTC, a pattern that resembles normal thyroid tissue. These data are consistent with the observed indolent biological behaviour and favourable prognosis associated with NIFTP, which lacks BRAF V600E mutations. Of note, next-generation thyroid oncological panel sequencing could not distinguish the thyroid cancer histotypes in our study cohort. In summary, our data suggest that 3D nuclear architecture can be a powerful analytical tool to diagnose and guide the clinical management of NIFTP.

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Changes in Nuclear Orientation Patterns of Chromosome 11 during Mouse Plasmacytoma Development

Cited by 4 publications

References 34 publications

XPO1 Inhibition Preferentially Disrupts the 3D Nuclear Organization of Telomeres in Tumor Cells

XPO1 Inhibition Preferentially Disrupts the 3D Nuclear Organization of Telomeres in Tumor Cells

The three‐dimensional cancer nucleus

3D nuclear architecture distinguishes thyroid neoplastic histotypes

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