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About the Authors:
Barbara J. Davis
Affiliation: Biomedical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, United States of America
John I. Risinger
Affiliation: Obstetrics Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, United States of America
Gadisetti V. R. Chandramouli
Affiliation: Obstetrics Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, United States of America
Pierre R. Bushel
Affiliation: Biostatistics Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, United States of America
Donna Day Baird
Affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, United States of America
Shyamal D. Peddada
* E-mail: [email protected]
Affiliation: Biostatistics Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, United States of America
Introduction
Uterine leiomyoma is a common, benign, monoclonal, diploid smooth muscle tumor with a frequent mutation in mediator complex subunit 12 (MED12) [1]. The development of this tumor is dependent on the presence of ovarian hormones, and women typically develop multiple leiomyomata over their reproductive lifespan. Leiomyomata become subclinical and regress after menopause. Based on these characteristics, we expected that leiomyomata would demonstrate homogeneous patterns of growth relative to the menstrual cycle and would provide a useful model by which to understand mechanisms of hormone-dependent tumor growth. Instead, in a longitudinal MRI-based study of leiomyoma growth (The Fibroid Growth Study) we found that leiomyomata are heterogeneous in nature and exhibit autonomous patterns of growth]. For example, leiomyoma growth rates ranged from −89% to +138% volume change over a 6 month interval and individual growth rates were variable among different tumors within the same woman. Growth rates of individual leiomyomata were also independent of tumor size, intrauterine location or the hormonal environment of the woman [2]. Moreover, their short-term patterns of growth revealed that many tumors exhibited growth spurts, followed by a period of no growth or spontaneous regression. Concurrent growth and regression in different tumors from the same woman could be seen [3].
This heterogeneous and variable behavior of tumors has significant consequences for translating physical information gained from the in-life study to a tissue-based molecular analysis of tumor growth. That is, despite having knowledge...