Expression profiling of uterine leiomyomata cytogenetic subgroups reveals distinct signatures in matched myometrium: transcriptional profilingof the t(12;14) and evidence in support of predisposing genetic heterogeneity.

Uterine leiomyomata (UL), the most common neoplasm in reproductive-age women, are classified into distinct genetic subgroups based on recurrent chromosome abnormalities. To develop a molecular signature of UL with t(12;14)(q14-q15;q23-q24), we took advantage of the multiple UL arising as independent clonal lesions within a single uterus. We compared genome-wide expression levels of t(12;14) UL to non-t(12;14) UL from each of nine women in a paired analysis, with each sample weighted for the percentage of t(12;14) cells to adjust for mosaicism with normal cells. This resulted in a transcriptional profile that confirmed HMGA2, known to be overexpressed in t(12;14) UL, as the most significantly altered gene. Pathway analysis of the differentially expressed genes showed significant association with cell proliferation, particularly G1/S checkpoint regulation. This is consistent with the known larger size of t(12;14) UL relative to karyotypically normal UL or to UL in the deletion 7q22 subgroup. Unsupervised hierarchical clustering demonstrated that patient variability is relatively dominant to the distinction of t(12;14) UL compared with non-t(12;14) UL or of t(12;14) UL compared with del(7q) UL. The paired design we employed is therefore important to produce an accurate t(12;14) UL-specific gene list by removing the confounding effects of genotype and environment. Interestingly, myometrium not only clustered away from the tumors, but generally separated based on associated t(12;14) versus del(7q) status. Nine genes were identified whose expression can distinguish the myometrium origin. This suggests an underlying constitutional genetic predisposition to these somatic changes which could potentially lead to improved personalized management and treatment.

Knowledge and likelihood to recommend intrauterine devices for adolescents among school-based health center providers.

PURPOSE: The American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention recommend intrauterine devices (IUDs) as safe and highly effective contraceptives for adolescents. Nevertheless, many U.S. providers do not recommend or provide IUDs to adolescents-a population at high risk for unintended pregnancy. The purpose of this study was to identify barriers to IUD provision for adolescents. METHODS: A 36-item self-administered survey of knowledge and attitudes regarding IUDs was completed by 162 staff of New York City school-based health centers, including 69 clinicians (e.g., pediatricians and nurse practitioners) and 93 nonclinicians (e.g., social workers and health educators). RESULTS: Half (55%) of all respondents would be likely to recommend an IUD to a patient under age 20 years. Respondents were less likely to recommend an IUD for patients with history of recent STD (31%), remote pelvic inflammatory disease (37%), and patients not in a monogamous relationship (38%). Whereas 77% of respondents indicated that IUDs are safe for adolescents, 18% of those respondents would be unlikely to recommend an IUD to a patient under age 20 years. While 86% of respondents knew that IUDs can be used in nulliparous women, 25% of those respondents would be unlikely to recommend an IUD to a patient who has never been pregnant. Additionally, 61% believed that counseling patients about IUDs would take more time than other methods. CONCLUSIONS: Misinformation about risks associated with IUDs and beliefs about patient eligibility may present barriers to provision. Apparent contradictions between knowledge and likelihood to recommend IUDs warrant further study.