Gene Expression in Uterine Leiomyoma from Tumors Likely to Be Growing (from Black Women over 35) and Tumors Likely to Be Non-Growing (from White Women over 35)

Barbara J Davis,John I Risinger,Pierre R Bushel,Shyamal D Peddada,Donna Day Baird,Gadisetti V R Chandramouli,Annie N Y Cheung

doi:10.1371/journal.pone.0063909

Abstract

The study of uterine leiomyomata (fibroids) provides a unique opportunity to investigate the physiological and molecular determinants of hormone dependent tumor growth and spontaneous tumor regression. We conducted a longitudinal clinical study of premenopausal women with leiomyoma that showed significantly different growth rates between white and black women depending on their age. Growth rates for leiomyoma were on average much higher from older black women than for older white women, and we now report gene expression pattern differences in tumors from these two groups of study participants. Total RNA from 52 leiomyoma and 8 myometrial samples were analyzed using Affymetrix Gene Chip expression arrays. Gene expression data was first compared between all leiomyoma and normal myometrium and then between leiomyoma from older black women (age 35 or older) and from older white women. Genes that were found significant in pairwise comparisons were further analyzed for canonical pathways, networks and biological functions using the Ingenuity Pathway Analysis (IPA) software. Whereas our comparison of leiomyoma to myometrium produced a very large list of genes highly similar to numerous previous studies, distinct sets of genes and signaling pathways were identified in comparisons of older black and white women whose tumors were likely to be growing and non-growing, respectively. Key among these were genes associated with regulation of apoptosis. To our knowledge, this is the first study to compare two groups of tumors that are likely to have different growth rates in order to reveal molecular signals likely to be influential in tumor growth.

Highlights

Uterine leiomyoma is a common, benign, monoclonal, diploid smooth muscle tumor with a frequent mutation in mediator complex subunit 12 (MED12) [1]
Using the gene expression data, comparisons were made between all leiomyomata compared to all myometrium and between tumors categorized by age/ethnicity as likely to be growing and non-growing
Ionotropic glutamate receptor AMPA2 (GRIA2) was the most highly upregulated gene in leiomyoma compared to myometrium, consistent with studies conducted by Tsibris [4]

Summary

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. Growth rates of individual leiomyomata were independent of tumor size, intrauterine location or the hormonal environment of the woman [2]. Their shortterm 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]

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Conclusion