Deletion 7q22 in uterine leiomyoma: A cytogenetic review

doi:10.1016/0165-4608(93)90195-R

Cancer Genetics and Cytogenetics

Volume 71, Issue 1, November 1993, Pages 1-6

https://doi.org/10.1016/0165-4608(93)90195-R Get rights and content

Abstract

The cytogenetic patterns of uterine leiomyomas have been extensively investigated, and cases characterized by specific clonal changes have been documented in detail. In these tumors one of the cytogenetic changes frequently observed has been a del(7), particularly del(7)(q22), usually as a sole anomaly. This is confirmed by our experience and by reports in the literature. The fact that del(7) is one of the most common abnormalities in leiomyoma raises the question of its role in tumor development. The main purpose of this review is to analyze the above aspect and to interpret its possible meaning. Our findings on cytogenetic abnormalities of chromosome 7 in leiomyoma, together with those reported in the literature, are reviewed and discussed. A listing of the genes located at 7q22 is also presented.

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Citation Excerpt :
Detailed sequence analysis of a region encompassing ∼500 bp upstream to ∼500 bp downstream of the breakpoint on chromosome 2 resulted in 179 putative transcription factor binding sites (data not shown), including four Cut-like homeodomain binding sites, three CCAAT-binding sites, eight muscle-specific binding sites, a p53-binding site, and an AT-rich binding site. The Cut-like homeodomain binding sites and the CCAAT-binding sites might link the cytogenetically defined leiomyoma subgroup with t(1;2)(p36;p24) to the subgroup with del(7)(q22), because in the latter subgroup the CCAAT replacement protein CUTL1 has been located within the deletion interval [26–29]. CUTL1, a member of the homeodomain family of DNA binding proteins, may regulate gene expression, morphogenesis, and differentiation and may also play a role in cell cycle progression [30–32].
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Cux (Cut homeobox) genes are present in all metazoans. Early reports described many phenotypes caused by cut mutations in Drosophila melanogaster. In vertebrates, CUX1 was originally characterized as the CCAAT-displacement protein (CDP). Another line of investigation revealed the presence of CUX1 within a multi-protein complex called the histone nuclear factor D (HiNF-D). Recent studies led to the identification of several CUX1 isoforms with distinct DNA binding and transcriptional properties. While the CCAAT-displacement activity was implicated in the transcriptional repression of several genes, some CUX1 isoforms were found to participate in the transcriptional activation of some genes. The expression and activity of CUX1 was shown to be regulated through the cell cycle and to be a target of TGF-beta signaling. Mechanisms of regulation include alternative transcription initiation, proteolytic processing, phosphorylation and acetylation. Cell-based assays have established a role for CUX1 in the control of cell cycle progression, cell motility and invasion. In the mouse, gene inactivation as well as over-expression in transgenic mice has revealed phenotypes in multiple organs and cell types. While some phenotypes could be explained by the presumed functions of CUX1 in the affected cells, other phenotypes invoked non-cell-autonomous effects that suggest regulatory functions with an impact on cell–cell interactions. The implication of CUX1 in cancer was suggested first from its over-expression in primary tumors and cancer cell lines and was later confirmed in mouse models.
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Analyses of uterine leiomyomata have shown cytogenetic heterogeneity. A commonly reported abnormality is an interstitial deletion involving breakpoints between 7q21 and 7q36 [3]. A relatively high frequency of deletions at 7q22 suggests the existence of a tumor suppressor gene in this region [4].
Uterine leiomyomata are benign, smooth-muscle tumors. The tumors are very common, affecting ∼10–15 million women in the United States annually. Uterine leiomyomata are often asymptomatic, but may cause symptoms that range in severity from mild abdominal discomfort to uterine prolapse. Several different chromosomal aberrations have been found in the tumor tissue. Because of the common occurrence of this tumor and the potential severity of associated sequelae, research delineating the different molecular subtypes is needed. Deletions on the long arm of chromosome 7 are believed to be the most common genetic anomaly in uterine leiomyoma. The size of the deletion varies, which makes it difficult to identify the genes that, upon deletion, contribute to tumor growth. The smallest previously defined interval was >12,000 kb. We have narrowed a minimal region to an interval of <500 kb.

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^☆: This work was supported by Grant CA 41183 from the National Cancer Institute, and by The Samuel and Ema Winters Foundation.

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Lead articleDeletion 7q22 in uterine leiomyoma: A cytogenetic review☆

Abstract

Cancer Genet Cytogenet

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Blood

Human Genet

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Genomics

Biochem Biophys Res Commun

Genomics

J Biol Chem

Lead article
Deletion 7q22 in uterine leiomyoma: A cytogenetic review☆