7q deletion mapping and expression profiling in uterine fibroids

doi:doi:10.1038/sj.onc.1208784

Oncogene (2005) 24, 6545–6554. doi:10.1038/sj.onc.1208784; published online 6 June 2005

7q deletion mapping and expression profiling in uterine fibroids

Sakari Vanharanta¹, Noel C Wortham², Päivi Laiho¹, Jari Sjöberg³, Kristiina Aittomäki⁴, Johanna Arola⁵, Ian P Tomlinson², Auli Karhu¹, Diego Arango¹ and Lauri A Aaltonen¹

¹Department of Medical Genetics, University of Helsinki, PO Box 63 (Haartmaninkatu 8), Biomedicum Helsinki, FIN-00014, Finland
²Molecular and Population Genetics Laboratory, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
³Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, PO Box 22 (Haartmaninkatu 2), FIN-00029, Finland
⁴Department of Clinical Genetics, Helsinki University Central Hospital, PO Box 140 (Haartmaninkatu 2 B), FIN-00029, Finland
⁵Department of Pathology, University of Helsinki, PO Box 21 (Haartmaninkatu 3), FIN-00014, Finland

Correspondence: LA Aaltonen, Department of Medical Genetics, Haartman Institute, University of Helsinki, Biomedicum Helsinki, Room B520A, PO Box 63 (Haartmaninkatu 8), FIN-00014, Finland. E-mail: lauri.aaltonen@helsinki.fi

Received 25 November 2004; Revised 18 March 2005; Accepted 21 April 2005; Published online 6 June 2005.

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Abstract

Uterine fibroids are some of the most common tumours of females, but relatively little is known about their molecular basis. Several studies have suggested that deletions on chromosome 7q could have a role in fibroid formation. We analysed 165 sporadic uterine fibroids to define a small 3.2 megabase (Mb) commonly deleted region on 7q22.3–q31.1, flanked by clones AC005070 and AC007567. We also used oligonucleotide microarrays to compare the expression profiles of 10 samples of normal myometrium and 15 fibroids, nine of which displayed 7q-deletions. Activating transcription factor 3, patched homolog (Drosophila), homeo box A5, death-associated protein kinase 1, and retinoic acid receptor responder 3 were downregulated, and excision repair crosscomplementing 3, transcription factor AP-2 gamma and protein kinase C beta 1 were upregulated in fibroids. New pathways were discovered related to fibroid formation. The presence or absence of 7q-deletions did not dramatically affect the global expression pattern of the tumours; changes, however, were observed in genes related to vesicular transport and nucleic acid binding.