{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:24:28Z","timestamp":1791141868193,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,11,18]],"date-time":"2005-11-18T00:00:00Z","timestamp":1132272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The naevoid basal cell carcinoma syndrome (NBCCS) is caused by mutations in the hedgehog receptor <jats:italic>PTCH<\/jats:italic> gene. It is characterized by developmental defects and a predisposition to the development of certain tumours, such as basal cell carcinoma, medulloblastoma and meningioma, and potentially fetal rhabdomyomas and embryonal rhabdomyosarcomas. This study aimed to analyse <jats:italic>PTCH<\/jats:italic> status in an NBCCS patient with fetal rhabdomyoma and to investigate whether deregulation of hedgehog signalling, as shown by altered expression of hedgehog pathway components and\/or genetic imbalances, is a general finding in sporadic rhabdomyomas and rhabdomyosarcomas. The NBCCS patient had a novel <jats:italic>PTCH<\/jats:italic> germ\u2010line mutation, 1370insT, and developed a fetal rhabdomyoma that harboured a 30 bp in\u2010frame deletion in the second allele resulting in homozygous inactivation of <jats:italic>PTCH<\/jats:italic>. Sporadic rhabdomyomas and rhabdomyosarcomas showed overexpression of <jats:italic>PTCH<\/jats:italic> (43\/43) and <jats:italic>GLI1<\/jats:italic> (41\/43) mRNA, as determined by <jats:italic>in situ<\/jats:italic> hybridization, indicating ongoing active hedgehog signalling. Immunohistochemical staining revealed a subgroup of fetal rhabdomyomas and embryonal rhabdomyosarcomas (12\/34) lacking PTCH immunoreactivity. Four of nine informative fetal rhabdomyomas and embryonal rhabdomyosarcomas showed loss of heterozygosity (LOH) in the <jats:italic>PTCH<\/jats:italic> region with two of these (one fetal rhabdomyoma and one embryonal rhabdomyosarcoma) also showing LOH in the <jats:italic>SUFU<\/jats:italic> region. These findings suggest that haploinsufficiency for the two tumour suppressor genes <jats:italic>PTCH<\/jats:italic> and <jats:italic>SUFU<\/jats:italic>, which are both active in the same signalling pathway, may be important for tumour development. Based on our results we propose that the pathogenesis of rhabdomyoblastic tumours, particularly fetal rhabdomyomas and embryonal rhabdomyosarcomas, involves deregulation of the hedgehog signalling pathway. Copyright \u00a9 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.1882","type":"journal-article","created":{"date-parts":[[2005,11,18]],"date-time":"2005-11-18T07:46:36Z","timestamp":1132299996000},"page":"17-25","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":191,"title":["Deregulation of the hedgehog signalling pathway: a possible role for the <i>PTCH<\/i> and <i>SUFU<\/i> genes in human rhabdomyoma and rhabdomyosarcoma development"],"prefix":"10.1002","volume":"208","author":[{"given":"Ulrica","family":"Tostar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl Johan","family":"Malm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne M","family":"Meis\u2010Kindblom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars\u2010Gunnar","family":"Kindblom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rune","family":"Toftg\u00e5rd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Birgitte","family":"Und\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,11,18]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"141","volume-title":"World Health Organization Classification of Tumours Pathology and Genetics. 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