Telomere shortening in uterine leiomyomas

Bonatz, G.; Frahm, Sven Olaf; Andreasa, Susann; Heidorn, Klaus; Jonat, W.; Parwaresch, Reza

doi:10.1016/s0002-9378(98)70050-x

Cited by 29 publications

(18 citation statements)

References 23 publications

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“…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. In another study, Rogalla et al 24 showed that telomere lengths in uterine leiomyomas decreased on average 83 base pairs with each successive cell division.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis

et al. 2006

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“…As with most normal human somatic cells, most benign neoplasms studied thus far, including uterine leiomyoma, have no telomerase activity. In fact the shortened telomeres found in leiomyomas when compared with adjacent normal myometrium in one study (Bonatz et al, 1998) demonstrates that these benign neoplasms are able to maintain their abnormal growth pattern without the aid of telomerase. Because an altered growth pattern already exists in these cells, however, transition to an oncogenic phenotype upon induction of telomerase activity could be easier in the leiomyoma cells than in normal somatic cells.…”

Section: Discussionmentioning

confidence: 99%

Immortalization of Human Uterine Leiomyoma and Myometrial Cell Lines After Induction of Telomerase Activity: Molecular and Phenotypic Characteristics

Carney

Tahara

Swartz

et al. 2002

Laboratory Investigation

125

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“…(Baird et al, 2003) Genetic epidemiology studies to date have been largely limited to small-scale or single marker studies of steroid hormones, particularly estrogen, as it is potentially the most critical regulator of fibroid growth. (Flake et al, 2003) Also other growth factors,(Sozen and Arici, 2002) reproductive factors,(Parazzini et al, 1996) dysregulation of microRNAs,(Marsh et al, 2008) shortening of telomeres,(Bonatz et al, 1998) excessive production of disorganized extracellular matrix,(Malik et al, 2010;Sozen and Arici, 2002) and acquired chromosomal aberrations have been noted in UF studies. (El-Gharib and Elsobky, 2010)…”

Section: Introductionmentioning

confidence: 99%

BET1L and TNRC6B associate with uterine fibroid risk among European Americans

et al. 2013

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Uterine fibroid (UFs) affect 77% of women by menopause and account for $9.4 billion in healthcare costs each year. Although UFs are heritable, genetic risk is poorly understood. The first genome-wide association study (GWAS) of UFs was recently performed in a Japanese population, with reported genome-wide significance for single nucleotide polymorphisms (SNPs) across three chromosomal regions. We tested these SNPs for association with UFs in U.S. cohorts. Women were enrolled in the Right from the Start (RFTS) cohort and the BioVU DNA repository. UF status in both cohorts was determined by pelvic imaging. We tested 65 candidate and haplotype-tagging SNPs for association with UFs presence using logistic regression in RFTS and the top three GWAS associated SNPs in BioVU. We also combined association results from both cohorts using meta-analysis. 1,086 European American (EA) cases and 1,549 controls were examined. Two SNP associations replicated (blocked early in transport 1 homolog[BET1L] rs2280543, RFTS-BioVU meta-odds ratio[OR]=0.67 95% confidence interval[CI] 0.38 to 0.96, Q=0.70, I=0, p=6.9×10-3; trinucleotide repeat containing 6B[TNRC6B] rs12484776, RFTS-BioVU meta-OR=1.21, 95% CI 1.07 to 1.35, Q=0.24, I=28.37, p=8.7×10-3). Meta-analyses combining evidence from RFTS, BioVU, and prior GWAS showed little heterogeneity in effect sizes across studies, with meta-p-values between 7.45×10-8 to 3.89×10-9, which were stronger than prior GWAS and supported associations observed for all previously identified loci. These data suggest common variants increase risk for UF in both EA and Japanese populations. However, further research is needed to assess the role of these genes across other racial groups.

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Telomere shortening in uterine leiomyomas

Cited by 29 publications

References 23 publications

Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis

Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis

Immortalization of Human Uterine Leiomyoma and Myometrial Cell Lines After Induction of Telomerase Activity: Molecular and Phenotypic Characteristics

BET1L and TNRC6B associate with uterine fibroid risk among European Americans

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