X-chromosomal inactivation analysis of uterine leiomyomas reveals a common clonal origin of different tumor nodules in some multiple leiomyomas

Cai, Yiran; Diao, Xiaoli; Wang, Shufang; Zhang, Wei; Zhang, Hong-Tu; Su, Qin

doi:10.3892/ijo.31.6.1379

Cited by 13 publications

(11 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We demonstrated that fibroids within the same woman often have different growth rates despite having a similar hormonal milieu. Indeed, each tumor appeared to have its own intrinsic growth rate, consistent with studies showing that fibroids are monoclonal in origin (15,16) with variable molecular characteristics (17)(18)(19)(20)(21). The only other large study of fibroid growth was conducted in Japan, and most of the 70 participants had only a single tumor (11); thus, variation in growth of fibroids from the same woman could not be evaluated.…”

Section: Discussionsupporting

confidence: 54%

Growth of uterine leiomyomata among premenopausal black and white women

Peddada

Laughlin

Miner

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

315

227

View full text Add to dashboard Cite

Uterine leiomyomata (fibroids) are the leading cause of hysterectomy in the United States. Black women have a greater fibroid burden than whites, yet no study has systematically evaluated the growth of fibroids in blacks and whites. We prospectively tracked growth for 262 fibroids (size range: 1-13 cm in diameter) from 72 premenopausal participants (38 blacks and 34 whites). Fibroid volume was measured by computerized analysis of up to four MRI scans over 12 months. We used mixed effects models to identify factors that are associated with growth, and results were converted to percent change per 6 months for clinical relevance. The median growth rate was 9% (range: ؊89% to ؉138%). Seven percent of fibroids regressed (>20% shrinkage). Tumors from the same woman grew at different rates (within-woman component of variation was twice the component among women; both were significant, P < 0.001). Black and white women less than 35 years of age had similar fibroid growth rates. However, growth rates declined with age for whites but not for blacks (P ‫؍‬ 0.05). The odds of a tumor growing more than 20% in 6 months also decreased with age for whites but not for blacks (P < 0.01). Growth rates were not influenced by tumor size, location, body mass index, or parity. We conclude that (i) spontaneous regression of fibroids occurs; (ii) fibroids from the same woman grow at different rates, despite a uniform hormonal milieu; (iii) fibroid size does not predict growth rate; and (iv) age-related differences in fibroid growth between blacks and whites may contribute to the higher symptom burden for black women.ethnic ͉ fibroid ͉ MRI ͉ tumor growth ͉ longitudinal data U terine leiomyomata (fibroids) are the leading indication for hysterectomy in the United States (1). Myomectomy and uterine artery embolization are also common treatments, but hysterectomy may be required subsequently (2). Hartmann et al. (3) estimate a $4,600 excess health care cost during the year following each US woman's diagnosis of fibroids. National medical costs associated with fibroids exceed 2 billion dollars annually (4). African Americans have a higher fibroid incidence (5, 6), experience more severe symptoms (7), present with larger tumors (7), and have a threefold higher risk of hysterectomy (8) compared with whites. Symptoms increase with the size of fibroids (7, 9, 10). However, few studies have examined the growth of fibroids over time (11-13), and no study has systematically followed the growth of fibroids in black and white women.The Fibroid Growth Study was designed to measure the growth of fibroids in black and white women with clinically relevant fibroids using MRI technology. We compare growth rates of individual tumors from the same woman; contrast fibroid growth in black and white women; and examine associations with age, parity, body mass index (BMI), and tumor characteristics. ResultsStudy Participants. Characteristics of the 72 participants are shown in Table 1. Our cohort ranged in age from 24 to 54 years, and approximately half were Afri...

show abstract

Section: Discussionsupporting

confidence: 54%

Growth of uterine leiomyomata among premenopausal black and white women

Peddada

Laughlin

Miner

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

315

227

View full text Add to dashboard Cite

show abstract

“…Several genetic studies based on the unique isoenzyme pattern (7, 8), X-inactivation (9, 10) and DNA methylation-sensitive HUMARA assay (11) have demonstrated that uterine fibroids are monoclonal in origin. Accordingly, some studies have proposed that these benign tumors could originate from a single dysregulated myometrial smooth muscle stem cell, under the influence of ovarian hormones (6, 12, 13).…”

Section: Introductionmentioning

confidence: 99%

Stro-1/CD44 as putative human myometrial and fibroid stem cell markers

Mas

Nair

Laknaur

et al. 2015

Fertility and Sterility

View full text Add to dashboard Cite

Objective To identify and characterize myometrial/fibroid stem cells by specific stem cell markers in human myometrium, and to better understand the stem cell contribution in the development of uterine fibroids. Design Prospective experimental human and animal study. Setting University research laboratory. Patients Women undergoing hysterectomy for treatment of symptomatic uterine fibroids. Animals Female NOD/SCID/IL-2Rγnull mice. Interventions Identification and isolation of stem cells from human fibroids (F) and adjacent myometrium (MyoF) tissues using Stro-1/CD44 specific surface markers. Main Outcome Measures Flow cytometry, semi- quantitative polymerase chain reaction, clonogenicity assays, cell culture, molecular analysis, immunocyto- histochemistry, in vitro differentiation, and xenotransplantation assays. Results Using Stro-1/CD44 surface markers, we were able to isolate stem cells from MyoF and F tissues. The undifferentiated status of isolated cells was confirmed by the expression of ABCG2 transporter, as well as additional stem cell markers OCT4, NANOG and GDB3, and the low expression of steroid receptors ERα and PR-A/PR-B. Mesodermal cell origin was established by the presence of typical mesenchymal markers (CD90, CD105, and CD73) and absence of hematopoietic stem cell markers (CD34, CD45), and confirmed by the ability of these cells to differentiate in vitro into adipocytes, osteocytes and chondrocytes. Finally, their functional capability to form fibroid-like lesions was established in xenotransplantation mouse model. The injected cells labeled with superparamagnetic iron oxide (SPIO) were tracked by both magnetic resonance imaging (MRI) and fluorescence imaging, thus demonstrating the regenerative potential of putative fibroid stem cells in vivo. Conclusion We have demonstrated that Stro-1/CD44 can be used as specific surface markers to enrich a subpopulation of myometrial/fibroids cells, exhibiting key features of stem/progenitor cells. These findings offer a useful tool to better understanding the initiation of uterine fibroids, and may lead the establishment of effective therapeutic options.

show abstract

“…Human uterine fibroids are clonal in origin, as confirmed by studying the inactivation of heterozygous-status alleles on the X chromosome [11]. Additionally, recent studies have confirmed that the different cell types contained in fibroids (mainly smooth muscle cells and fibroblasts) are all clonally derived from a parental cell with implied multipotent stem cell properties [12].…”

Section: Cellular Origin Of Fibroids: Candidate Cells For the Developmentioning

confidence: 88%

“…Moreover, the introduction of let-7 microRNA in cultures of cells from these large myomas (with relative HMGA2 overexpression) resulted in a reduction of HMGA2 protein. However, it is hard to imagine that in vivo regulation of HMGA2 by let-7 has a specific functional role in fibroids or is the only factor contributing to tumor genesis and growth [11,31].…”

Section: Translocation T(12;14) (Q14-15;q23-24) Hmga2 and Rad5ibmentioning

confidence: 99%

Uterine Fibroids Review: Understanding their Origins to Better Understand their Future Treatments

Botía¹,

Camarasa²,

Baixauli³

et al. 2017

J Tumor Res

View full text Add to dashboard Cite

Despite the high prevalence and the enormous impact the uterine fibroids has on the healthcare system and the economy, there is no effective medical treatment available to eliminate fibroids. This is due in part to the fact that very little is known about their pathophysiology; in order to look for and potentially find treatments capable of eliminating fibroids; we must gain a deep understanding of the mechanisms behind their initiation, stimulation and growth. In this article, we comprehensively review current knowledge of the pathogenesis of uterine fibroids, with the aim of better understanding their origin, as well as discussing the action of already existing medical treatments in order to highlight ways that potential future therapies may be able to target the disease. A literature search was performed in PubMed to find articles related to the etiopathogenesis of fibroids and their treatments. Myomas comprise areas of disordered smooth muscle fascicles characterized by an excess of a cellular extracellular matrix (ECM) with a deregulated phenotype. Although the initial event is believed to be smooth muscle cell proliferation, it is thought that a complex signalling system is also necessary. Non-hormonal factors may be responsible for initiating the development of uterine fibroids, although hormonal stimulation is an essential factor for their growth. Recent studies have confirmed that the different cell types contained in fibroids are all clonally derived from a parental cell with implied multipotent stem cell properties. Ethnicity also strongly influences the development and clinical severity of fibroids. Many Growth factors and their respective receptors have been implicated in fibroid growth. The available evidence continues to reinforce the importance of progesterone in the development of fibroids. The Ulipristal Acetate mediated volume reduction is due to a series of multifactorial and successive events that lead to a low proliferation rate.

show abstract

X-chromosomal inactivation analysis of uterine leiomyomas reveals a common clonal origin of different tumor nodules in some multiple leiomyomas

Cited by 13 publications

References 45 publications

Growth of uterine leiomyomata among premenopausal black and white women

Growth of uterine leiomyomata among premenopausal black and white women

Stro-1/CD44 as putative human myometrial and fibroid stem cell markers

Uterine Fibroids Review: Understanding their Origins to Better Understand their Future Treatments

Contact Info

Product

Resources

About