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Title: Identification of CUX1 as the recurrent chromosomal band 7q22 target gene in human uterine leiomyoma
Authors: Schoenmakers, Eric F P M ×
Bunt, Jens
Hermers, Lianne
Schepens, Marga
Merkx, Gerard
Janssen, Bert
Kersten, Monique
Huys, Erik
Pauwels, Patrick
Debiec-Rychter, Maria
van Kessel, Ad Geurts #
Issue Date: Jan-2013
Publisher: Wiley-Liss, Inc.
Series Title: Genes, chromosomes & cancer vol:52 issue:1 pages:11-23
Article number: 10.1002/gcc.22001
Abstract: Uterine leiomyomas are benign solid tumors of mesenchymal origin which occur with an estimated incidence of up to 77% of all women of reproductive age. The majority of these tumors remains symptomless, but in about a quarter of cases they cause leiomyoma-associated symptoms including chronic pelvic pain, menorrhagia-induced anemia, and impaired fertility. As a consequence, they are the most common indication for pre-menopausal hysterectomy in the USA and Japan and annually translate into a multibillion dollar healthcare problem. Approximately 40% of these neoplasms present with recurring structural cytogenetic anomalies, including del(7)(q22), t(12;14)(q15;q24), t(1;2)(p36;p24), and anomalies affecting 6p21 and/or 10q22. Using positional cloning strategies, we and others previously identified HMGA1, HMGA2, RAD51L1, MORF, and, more recently, NCOA1 as primary target (fusion) genes associated with tumor initiation in four of these distinct cytogenetic subgroups. Despite the fact that the del(7)(q22) subgroup is the largest among leiomyomas, and was first described more than twenty years ago, the 7q22 leiomyoma target gene still awaits unequivocal identification. We here describe a positional cloning effort from two independent uterine leiomyomas, containing respectively a pericentric and a paracentric chromosomal inversion, both affecting band 7q22. We found that both chromosomal inversions target the cut-like homeobox 1 (CUX1) gene on chromosomal band 7q22.1 in a way which is functionally equivalent to the more frequently observed del(7q) cases, and which is compatible with a mono-allelic knock-out scenario, similar as was previously described for the cytogenetic subgroup showing chromosome 14q involvement. © 2012 Wiley Periodicals, Inc.
URI: 
ISSN: 1045-2257
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Genetics of Malignant Disorders
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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