Uterine leiomyomas (ULs), or fibroids, are among the most common human neoplasms, occurring in an estimated 77% of women of childbearing age and causing symptoms in every fourth Caucasian woman. Although benign, ULs frequently cause a variety of health complications, and infertility, and form a major burden to women’s health. As consequence of high morbidity, ULs are the leading cause of hysterectomy worldwide and have a considerable socio-economic impact. The approximate annual societal costs reach $34 billion in the United States, which is more than the equivalent costs of colon and breast cancer combined, forming a major burden to women's health. Despite the high prevalence and socio-economic impact of ULs – possibly due to the non-malignant nature of these lesions – relatively little research using modern high-throughput technologies has been conducted on this important condition. To date, the molecular mechanisms underlying the growth and development of ULs remain largely unknown.
ULs are frequently found incidentally during a routine pelvic examination and the diagnosis is typically confirmed by ultrasound to differentiate these lesions from other pelvic conditions. None of the current treatment options take into account the possible existence of various UL subclasses, but the lesions are seen as a single entity. Several other factors including the size, number, and location of the tumors, as well as the symptoms and reproductive desires of the patient, are essential when selecting optimal treatment. Still today, surgery is the standard method for treating ULs. For now, hysterectomy is the only definitive solution that eliminates both the symptoms and chances of recurrence, but as an invasive procedure it is far from optimal and not suitable for women who have not completed childbearing. Myomectomy is an example of a uterus-sparing treatment option. This approach, however, is also invasive. Effective drug treatments against ULs are still lacking, and ULs remain both at present and in the near future a highly significant challenge for women’s health.
Although the precise molecular mechanisms underlying the genesis of ULs are still largely unknown, various factors, in addition to ovarian hormones, seem to participate in regulating the growth and development of these lesions, including genetic factors. During the last decade, high-throughput sequencing technologies have revolutionized the field of tumor genomics, enabling comprehensive genome-wide characterization of somatic alterations in a large number of tumor specimens. Our recent breakthrough findings, derived from the use of these technologies, led us to hypothesize that ULs can and should be classified based on their molecular background. However, the number of examined UL was previously relatively small and molecular classification of ULs had not gained ground even in research papers, thus our overall objective was to further define and characterize these subclasses, both molecularly and clinically, to increase the knowledge on UL genesis and to improve the management of the disease.
Through the main results we have achieved, we have advanced the research field significantly forward and we took the knowledge on ULs to a completely new level, being an important step towards non-invasive management of ULs. Our project resulted in novel discoveries of explicit scientific and clinical importance. In conclusion, these results have the potential to benefit hundreds of millions of women worldwide. Thus, the potential economic and societal impact of this research project are huge.
