title: Is loss of heterozygosity at 9q22.3 (PTCH gene) and 19p13.3 (STK11 gene) involved in the pathogenesis of ovarian stromal tumors?
abstract: Some ovarian fibromas and rare fibrosarcomas are associated with Gorlin syndrome, which is caused by mutation in the human homologue of Drosophila patched gene (PTCH), localized on chromosome 9q22.3. The relationship between PTCH gene and sporadic ovarian tumors in the thecoma-fibroma group has not been well characterized. On the other hand, we have recently described loss of heterozygosity (LOH) at 19p13.3 in 2 sporadic fibromas with sex-cord elements. We have analyzed DNA from 8 fibromas, 6 cellular fibromas, 2 fibrothecomas, 9 luteinized thecomas, and 2 fibrosarcomas of the ovary for LOH at 9q22.3 and 19p13.3, using polymerase chain reaction amplification for 10 microsatellite markers. LOH at 9q22.3 was detected in 4 (67%) of 6 cellular fibromas, with the highest frequency at microsatellite marker D9S15, which localizes proximal to the PTCH gene. Of 9 luteinized thecomas, 2 (22%) also exhibited LOH at 9q22.3 with 3 microsatellite markers other than D9S15. Allelic losses were not detected in any fibroma, fibrothecoma, or fibrosarcoma. LOH at 19p13.3 was found in 2 (25%) of 8 fibromas, 3 (50%) of 6 cellular fibromas, and 1 (11%) of 9 luteinized thecomas. None of the 2 fibrothecomas or 2 fibrosarcomas showed LOH at 19p13.3. LOH at both 9p22.3 and 19p13.3 was observed in 3 (50%) of 6 cellular fibromas, but not in luteinized thecomas. The results indicate that (1) LOH at both PTCH gene and STK11 gene is relatively frequent in cellular fibromas; (2) approximately a quarter of luteinized thecomas exhibited LOH of the PTCH gene; in both neoplasms, cellular fibromas and luteinized thecomas, LOH may play a role in their pathogenesis; and (3) sporadic cellular fibromas may arise through similar genetic pathways as cases of Gorlin syndrome.
authors.affiliation: Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, 08025 Barcelona, Spain.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsuji
authors.forename: Lluis
authors.initials: L
authors.lastname: Catasus
authors.forename: Jaime
authors.initials: J
authors.lastname: Prat
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000328:Adult; D000368:Aged; D001478:Basal Cell Nevus Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002888:Chromosomes, Human, Pair 19; D002899:Chromosomes, Human, Pair 9; D005260:Female; D005350:Fibroma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008184:Luteal Cells / Q000378:metabolism / Q000473:pathology; D014975:Lutein / Q000378:metabolism; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D013798:Thecoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D005819:Genetic Markers; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D014975:Lutein