Telomere Shortening and Associated Chromosomal Instability in Peripheral Blood Lymphocytes of Patients With Hodgkin’s Lymphoma Prior to Any Treatment Are Predictive of Second Cancers

M’Kacher, Radhia; Bennaceur-Griscelli, Annelise; Girinsky, T.; Koscielny, Serge; Delhommeau, François; Dossou, Joseph; Violot, D.; Leclercq, Evelyne; Courtier, Marie Hélène; Béron-Gaillard, Nadine; Assaf, Elias; Ribrag, Vincent; Bourhis, Jean; Feneux, D.; Bernheim, Alain; Parmentier, C; Carde, Patrice

doi:10.1016/j.ijrobp.2007.01.050

Cited by 63 publications

(62 citation statements)

References 30 publications

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“…Indeed, it is likely that we have underscored the number of complete translocations in our study and thus our results are conservative. Moreover, telomere alterations can be a source of chromosome instability and can result in complex chromosome rearrangements (M'Kacher et al, 2007). The introduction of PNA telomeric probes in future studies could clarify this issue.…”

Section: Resultsmentioning

confidence: 99%

“…Whole blood was added to the culture medium with 2% phytohaemagglutinin M (GIBCO/BRL, USA) for 72 h. Blood was incubated at 37 ° C for 2 h in the presence of colcemid (0.1 g/ml) before harvesting. Slides were prepared after standard methanol/acetic acid (3/1, v/v) fixation and stored at -20 ° C until use (M'Kacher et al, 2007). …”

Section: Cytogenetic Proceduresmentioning

confidence: 99%

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Elevated chromosome translocation frequencies in New Zealand nuclear test veterans

Wahab

Nickless

Najar-M’Kacher

et al. 2008

Cytogenet Genome Res

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In 1957/58 the British Government conducted a series of nuclear tests in the mid-Pacific codenamed Operation Grapple, which involved several naval vessels from Britain and New Zealand. Two New Zealand frigates with 551 personnel onboard were stationed at various distances between 20 and 150 nautical miles from ground zero. In the present study we applied the cytomolecular technique mFISH (multicolour fluorescent in situ hybridisation) to investigate a potential link between chromosome abnormalities and possible past radiation exposure in New Zealand nuclear test veterans who participated in Operation Grapple. Compared to age matched controls, the veterans showed significantly higher (P < 0.0001) frequencies of chromosomal abnormalities (275 translocations and 12 dicentrics in 9,360 cells vs. 96 translocations and 1 dicentric in 9,548 cells in the controls), in addition to a significant excess of CCRs (complex chromosomal rearrangements) in the veterans. A Kolmogorov-Smirnoff test showed that the distributions of translocations for the two groups were significantly different.

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Section: Resultsmentioning

confidence: 99%

Section: Cytogenetic Proceduresmentioning

confidence: 99%

Elevated chromosome translocation frequencies in New Zealand nuclear test veterans

Wahab

Nickless

Najar-M’Kacher

et al. 2008

Cytogenet Genome Res

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“…A decisive role of telomere shortening in the pathogenesis of HD and aggressive non-Hodgkin's lymphoma is also supported by the results of two recently completed prospective studies. 34,35 Moreover, very short telomeres have been shown to have a predisposition to structural and numerical aberrations in colon cancer 36 and other malignancies. [37][38][39] Since its original description as a framework structure, 40 it has become evident that the nuclear matrix is a highly organized 3D structure in which chromosomes occupy specific non-random territories.…”

mentioning

confidence: 99%

The 3D nuclear organization of telomeres marks the transition from Hodgkin to Reed–Sternberg cells

et al. 2008

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To get an insight into the transition from mononuclear Hodgkin cells (H cells) to diagnostic multinuclear Reed-Sternberg cells (RS cells), we performed an analysis of the three-dimensional (3D) structure of the telomeres in the nuclei of the Hodgkin cell lines HDLM-2, L-428, L-1236 and lymph node biopsies of patients with Hodgkin's disease. Cellular localization of key proteins of the telomere-localized shelterin complex, the mitotic spindle and double-stranded DNA breaks was also analyzed. RS cells show significantly shorter and significantly fewer telomeres in relation to the total nuclear volume when compared with H cells; in particular, telomere-poor 'ghost' nuclei are often adjacent to one or two nuclei displaying huge telomeric aggregates. Shelterin proteins are mainly cytoplasmic in both H and RS cells, whereas double-stranded DNA breaks accumulate in the nuclei of RS cells. In RS cells, multipolar spindles prevent proper chromosome segregation. In conclusion, a process of nuclear disorganization seems to initiate in H cells and further progresses when the cells turn into RS cells and become end-stage tumor cells, unable to divide further because of telomere loss, shortening and aggregate formation, extensive DNA damage and aberrant mitotic spindles that may no longer sustain chromosome segregation. Our findings allow a mechanistic 3D understanding of the transition of H to RS cells.

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“…Further investigation is necessary in order to draw safe conclusions. Finally, it is worth mentioning that a relationship was recently found between telomere shortening and development of second cancers in HL patients (M'Kacher et al 2007). Telomere dysfunction is linked to DNA repair and probably to decreased Ku70 expression, although further studies are required to elucidate the mechanism of telomere shortening in HL patients.…”

Section: Hodgkin's Lymphoma (Hl)mentioning

confidence: 81%

DNA Repair Deficiency Associated with Hematological Neoplasms

Economopoulou¹,

Pappa²,

Papageorgiou³

et al. 2011

DNA Repair and Human Health

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Telomere Shortening and Associated Chromosomal Instability in Peripheral Blood Lymphocytes of Patients With Hodgkin’s Lymphoma Prior to Any Treatment Are Predictive of Second Cancers

Cited by 63 publications

References 30 publications

Elevated chromosome translocation frequencies in New Zealand nuclear test veterans

Elevated chromosome translocation frequencies in New Zealand nuclear test veterans

The 3D nuclear organization of telomeres marks the transition from Hodgkin to Reed–Sternberg cells

DNA Repair Deficiency Associated with Hematological Neoplasms

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