Telomere Length and Human Telomerase Reverse Transcriptase Expression As Markers for Progression and Prognosis of Colorectal Carcinoma

Gertler, Ralf; Rosenberg, Robert D.; Stricker, Dominik; Friederichs, Jan; Hoos, Axel; Werner, Martin; Ulm, Kurt; Holzmann, Bernhard; Nekarda, H.; Siewert, J. R.

doi:10.1200/jco.2004.09.160

Cited by 162 publications

(197 citation statements)

References 29 publications

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“…However, the meaning of telomere length is a complicated subject. While it has been shown that telomere length correlates inversely, and telomerase activity directly, with malignancy in epithelial tumors, [6][7][8][9] only a couple of studies address this question in soft tissue tumors. 22,23 Bonatz et al measured telomere length in 107 uterine leiomyomas using a Southern blot method and found that telomeres were significantly shorter in tumoral tissue compared to adjacent uterine smooth muscle.…”

Section: Discussionmentioning

confidence: 99%

“…However, since there is a 50% chance that the same X-inactivation could occur incidentally between two tumors, more cases should be analyzed using this method. Telomere shortening, a possible crucial event leading to chromosomal instability and development of malignancy, has been reported in multiple types of human cancer [6][7][8][9] and can be demonstrated with telomerespecific fluorescence in situ hybridization (FISH) probes.…”

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confidence: 99%

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Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis

et al. 2006

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Benign metastasizing leiomyoma is a rare condition affecting women with a history of uterine leiomyomata and is characterized by multiple histologically benign pulmonary smooth muscle tumors. Speculations on its pathogenesis include a benign uterine leiomyoma colonizing the lung, a metastatic low-grade uterine leiomyosarcoma, and primary pulmonary leiomyomatosis. To elucidate its pathogenesis, we analyzed the clinical, pathological and immunohistochemical features, clonality, and telomere length of multiple lung and uterine tumors in three patients with benign metastasizing leiomyoma. In all cases, pulmonary tumors had benign histology and immunohistochemical profiles (estrogen receptor positive, progesterone receptor positive, and very low proliferative index) identical to uterine leiomyoma. In eight tumors from three patients, clonality was assessed by analyzing the variable length of the polymorphic CAG repeat sequence within the human androgen receptor gene. In the two informative patients pulmonary and uterine tumors showed identical patterns of androgen receptor allelic inactivation, indicating that they were clonal. The telomere length measured by fluorescence in situ hybridization in pulmonary leiomyomas of all three patients were either long or very long and were identical to the uterine counterparts, indicating significant telomere shortening is not a crucial step for developing metastases. Our evidence supports the notion that benign metastasizing leiomyoma is clonally derived from benign-appearing uterine leiomyomas.

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Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis

et al. 2006

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“…3B). Though previous studies have reported an association between hTERT expression levels and disease progression in colorectal cancer [47][48][49], these studies primarily looked at hTERT transcript levels. Here, 78% of colon tumours expressed hTERT protein, 8% of which had nuclear hTERT expression, similar levels of hTERT expression in colorectal tumours have been previously reported [50].…”

Section: Ruvbl2 Impacts Htert Activity and Associates With Htert Exprmentioning

confidence: 99%

RuvBl2 cooperates with Ets2 to transcriptionally regulate hTERT in colon cancer

et al. 2011

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Edited by Varda RotterKeywords: RuvBl2 hTERT c-Myc Colon cancer a b s t r a c t Human cancers utilise telomerase to maintain telomeres and prohibit cell senescence. Human telomerase reverse transcriptase (hTERT), an essential component of this complex, is regulated at the level of gene transcription. Using SILAC-proteomic analysis and molecular studies, we identified the AAA+ ATPase, RuvBl2 as a transcriptional regulator of hTERT and established that this regulation is through cooperation with Ets-2. In colon cancer patients, nuclear expression of RuvBl2 associated with nuclear expression of hTERT, pEts2 and advanced nodal disease (P < 0.01, P = 0.05 and P = 0.03 respectively, n = 170). These data firmly implicate RuvBl2 in Ets2 mediated regulation of hTERT in colon cancer which has functional and clinical consequences.

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“…For these reasons, numerous investigators have hypothesized that altered telomere length could predispose cells to possess the properties necessary to metastasize and cause recurrent disease, and thereby be a predictor of clinical outcome. [12][13][14][15][16][17][18][19][20][21][22][23][24] This concept is shown schematically in Figure 1.…”

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confidence: 99%

“…[8][9][10][11] This review summarizes the use of telomere length or its proxies, such as telomere content, as potential prognostic markers in solid tumors, a possibility that has been raised in the last decade by a number of investigators. [12][13][14][15][16][17][18][19][20][21][22][23][24] A corresponding comprehensive discussion of these promising developments has not yet been offered, in spite of the growing body of knowledge. Excluded from this discussion are numerous reports on the prognostic value of telomeres in hematological malignancies, a research area that, in contrast to solid tumors, has been addressed in more depth and previously reviewed.…”

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Telomeres: Prognostic markers for solid tumors

Bisoffi

Heaphy

Griffith

2006

Intl Journal of Cancer

101

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Solid tumors continue to affect millions of people worldwide. Increasingly sophisticated diagnostic tools contribute to the high incidence rates for some tumor types, and treatment options continue to expand. However, the progression of solid tumors represents a challenge for the appropriate treatment of individual patients because of the relative inaccuracy of current prognostic markers, including the widely used Tumor-Nodes-Metastasis (TNM) staging system, to predict the course of disease. As a result, both over-and undertreatment are clinical realities in the management of patients diagnosed with solid tumors. Therefore, populationbased screening programs that increase the overall cancer incidence rates are controversial, as they may do little to improve the patient's quality of life. Consequently, there is a strong need to develop novel and independent markers of prognosis. In this context, we review the use of telomeres as prognostic markers for solid tumors, including cancers from lung, breast, prostate, colon, brain and head and neck. Telomeric sequences, the repetitive DNA at the end of human chromosomes, are mediators of genomic stability and can undergo length alterations during tumor initiation and progression. In a number of studies reviewed here, these alterations, measured as telomere attrition and elongation, have been shown either to be associated with clinical markers of disease progression or to be independent markers of cancer prognosis. We conclude from these studies that careful assessment of telomere length or its proxies, such as telomere DNA content, will be part of novel risk assessment and prognostic modalities for patients with solid tumors. ' 2006 Wiley-Liss, Inc.

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Telomere Length and Human Telomerase Reverse Transcriptase Expression As Markers for Progression and Prognosis of Colorectal Carcinoma

Cited by 162 publications

References 29 publications

Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis

Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis

RuvBl2 cooperates with Ets2 to transcriptionally regulate hTERT in colon cancer

Telomeres: Prognostic markers for solid tumors

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