Naslov
Alterations of Patched May cause developmental malformations and cancer

Autori
Levanat, Sonja ; Crnić, Ivana ; Orešković, Slavko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of the 10th International Congress of Human Genetics ; u: European Journal of Human Genetics / Busquin, Philippe - Beč : ESHG, 2001, 112-112

Skup
International Congress of Human Genetics (10 ; 2002)

Mjesto i datum
Beč, Austrija, 15.05.2001. - 19.05.2001

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
patched; PTCH; tumor suppressor; NBCCS; LOH; SSCP; chromosomal region 9q22.3

Sažetak
Costitutional hemizygous inactivation of PTCH, the SHH/PTCH signaling pathway gene, which moderates SHH signaling, manifests itself as Nevoid Basal Cell Carcinoma Syndrome (NBCCS) or Golin syndrome, a condition variably characterized ba a number of developmental disorders and malformations, and by predisposition to certain malignancies where the most frequent are basal cell carcinomas, medulloblastomas and ovarian fibromas. The PTCH gene, a human homologue of the Drosophila segment polarity gene patched, maps to chromosome 9q22.3 and loss of heterozygosity (LOH) at this site in both sporadic and hereditary basal cell casrcinomas and medulloblastomas suggest that it functions as a tumor suppressor. Our studies of LOH in sporadic ovarian fibromas for the same region and aberrant SSCP pattern in sporadic ovarian fibromas contribute to the Ptch role in their genesisi as well. In our studies we used DNA from fresh tissues and blood leukocytes, which were typed for several short tandem repeat polymorphisms spanning chromosome 9q21-q31 and by SSCP analysis we have been analyzed variability in PTCH exons. LOH for the PTCH region has been found in odontogenic keratocysts, the cyst type with highly increased incidence in NBCCS. Suggestive temporal distribution of SHH signaling, recently observed during tooth development, lead us to invesigate its association with dentigerous cysts, the other major noninflammatory cyst of odontogenic origin. We report here that PTCH is inactivated in dentigerous cysts, the implication being the same for their genesis as well. More generally, PTCH alterations may prove to be a necessary, and perhaps the initiating event, in formation and growth of various noninflammatory cysts, especially with our observations of incomplete heterozygosity which we interpreted as LOH in this region for ovarian dermoid cysts. This would be consistent with our view that local PTCH inactivation can, under predisposing circumstances, lead to persistant though not by itself truly aggressive cell proliferation.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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