Changes in the expression of telomere maintenance genes suggest global telomere dysfunction in B-chronic lymphocytic leukemia

Poncet, Delphine; Belleville, Aurélie; Roodenbeke, Claire T'Kint de; Climens, Aude Roborel de; Simon, Elsa Ben; Merle‐Béral, Hélène; Callet‐Bauchu, Evelyne; Salles, Gilles; Sabatier, Laure; Delić, Jozo; Gilson, Éric

doi:10.1182/blood-2007-09-111245

Cited by 110 publications

(117 citation statements)

References 26 publications

(32 reference statements)

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“…At first glance, the finding that DKC1 is overexpressed in common carcinomas seems somewhat paradoxical, given that dyskerin-inactivating mutations in dyskeratosis congenita predispose to cancer development, and DKC1 is downregulated in sporadic CLL (Poncet et al, 2008). Moreover, a complete lack of dyskerin function is lethal.…”

Section: Discussionmentioning

confidence: 94%

“…Somewhat paradoxically, dyskeratosis congenita patients are also prone to develop cancers, particularly skin cancers and leukaemias. Moreover, in sporadic chronic lymphocytic leukaemia, DKC1 expression is diminished, together with that of other telomerase-associated factors (Poncet et al, 2008). It is debated as to loss of which function of dyskerin is most crucial for the symptoms of dyskeratosis congenita.…”

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confidence: 99%

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DKC1 overexpression associated with prostate cancer progression

et al. 2009

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BACKGROUND: Dyskerin encoded by the DKC1 gene is a predominantly nucleolar protein essential for the formation of pseudouridine in RNA and the telomerase RNA subunit hTR. Inherited mutations inactivating dyskerin cause dyskeratosis congenita, a syndrome with progeroid features characterised by skin defects and haematopoiesis failure, as well as cancer susceptibility. In this study, we report DKC1 overexpression in prostate cancers. METHODS: Expression of DKC1 was measured by quantitative RT -PCR in prostate cancer tissues in relation to hTR and the proliferation marker MKI67. Effects of dyskerin downregulation on proliferation, apoptosis and senescence of prostate cancer cell lines were determined. RESULTS: DKC1 was significantly overexpressed in prostate cancers, particularly in high-stage and recurring cases, correlating moderately with hTR and MKI67. Dyskerin downregulation in prostate carcinoma cell lines by siRNA diminished cell proliferation, but elicited neither apoptosis nor senescence. Apoptosis induction by TNF-a or tunicamycin was not enhanced. Long-term downregulation led predominantly to cell shrinking and loss of adhesion. INTERPRETATION: DKC1 upregulation in prostate cancers is common and likely to be necessary for extensive tumour growth. The phenotype of prostate carcinoma cell lines after dyskerin downregulation suggests that its most critical function is sustaining protein biosynthesis. Intriguingly, compromised function and overexpression of dyskerin can both contribute to cancer development.

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Section: Discussionmentioning

confidence: 94%

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confidence: 99%

DKC1 overexpression associated with prostate cancer progression

et al. 2009

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“…In addition, hPOT1 may involved in cell cycle regulation (Wu et al, 2006), apoptosis (Wan et al, 2011) and so on. Many studies had reported that hPOT1 is correlated with a broad range of cancers, for example, gastric cancer (Wan et al, 2011), papillary thyroid cancer (Cantara et al, 2012), breast cancer (Shen et al, 2010), leukemia (Poncet et al, 2008). Some reports centered in gene variations of hpot1.…”

Section: Expression Of Hpot1 In Hela Cells and The Probability Of Genmentioning

confidence: 99%

Expression of hPOT1 in HeLa Cells and the Probability of Gene Variation of hpot1 Exon14 in Endometrial Cancer are Much Higher than in Other Cancers

Liu

Pu²,

Huang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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To investigate the expression of hPOT1 in the HeLa cell line and screen point mutations of hpot1 in different tumor tissues a two step osmotic method was used to extract nuclear proteins. EMSA was performed to determine the expression of hPOT1 in the HeLa cell line. PCR was also employed to amplify the exon14 sequence of the hpot1 gene in various of cancer tissues. A SV gel and PCR clean-up system was performed to enrich PCR products. DNAStar was used to analyse the exon14 sequence of the hpot1 gene. hPOT1 was expressed in the HeLa cell line and the signal was gradually enhanced as the amount of extracted nuclear proteins increased. The DNA fragment of exon14 of hpot1 was successfully amplified in the HeLa cell line and all cancer tissues, point mutations being observed in 2 out of 3 cases of endometrial cancer (66.7%) despite the hpot1 sequence being highly conserved. However, the sequence of hpot1 exon14 do not demonstrate point mutations in most cancer tissues. Since hPOT1 was expressed in HeLa cell and the probability of gene point variants was obviously higher in endometrial cancer than other cancers, it may be involved in the pathogenesis of gynecological cancers, especially in cervix and endometrium.

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“…2 Changes in the expression of shelterin genes have recently been established in CLL by comparison to normal B cells, suggesting a global telomere dysfunction in B-CLL. 5 However, despite enhanced telomere shortening, no evidence of altered shelterin protein expression or binding of TRF1 and TRF2 at telomeres was observed between sensitive and resistant CLL cells. These results indicate that if shelterin dysfunction occurs in CLL, it cannot alone explain the differences in telomere length between indolent and refractory forms of the disease.…”

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confidence: 99%

“…The telomere length and telomerase activity are further prognostic markers as unfavourable disease was associated with short telomeres 4 (reviewed in Van Bockstaele et al 3 ). This, together with altered expression of several telomeric components, 5 indicates that telomeres are profoundly rearranged in CLL cells.…”

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confidence: 99%