In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 2144-2144
Abstract:
Uterine leiomyoma (UL) are tumors that arise from the uterine smooth muscle wall. Despite their nonmalignant nature, UL represent a major concern in women's health through their induction of significant morbidity in more than 25% of reproductive-age. The etiology of UL remains unknown. Cytogenetic studies have been identified recurrent aberrations involving the t(12;14); del(7)(q22q32); trisomy 12; and 6p21 rearrangements. The aim of this study was integrate genomic and gene expression microarray data to identify genes with altered function due to genomic instability. DNA and RNA were extracted from 24 UL from women at proliferative (n=14) and secretory (n=10) phase of the menstrual cycle. Normal control RNA was obtained from adjacent myometrium from all cases. Array CGH and gene expression microarray was done using the Human 44K Agilent oligoarrays according to manufacturer's instructions. Data were extracted and flagged with Feature Extraction software (version 10.1.1.1) and processed using Genomic Workbench Standard (version.5.0.14). Non-supervised analysis of gene expression revealed clustering of all cases independent of the phase of menstrual cycle. It was observed a significant correlation between deletion and down expression at 1q32.2-q44 and 7q11.22-q33. Although deletions at 1q and 7q had been described previously as involved in UL, the genes mapped at these regions were poorly studied. These genes are involved in Wnt signaling pathway, induction of apoptosis, transforming growth factor signaling pathway, fumarate hydratase activity, and fibrinolysis. Furthermore, it was observed correlation between amplification and increased gene expression at 11p15.5, 14q32.33, and 16p13.3. These regions harboring genes with function associated with regulation of cell proliferation and regulation of JNK cascade. Our results provide strong circumstantial evidence that different patterns of genomic imbalances contribute to their specific transcriptomic profiles. In the future, new therapies based on these findings can be applied in a subgroup of patients with specific genomic imbalances. Supported by the FAPESP (07/51643-8) and CNPq (485032/2007-4), Brazil. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2144.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-2144
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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