title: A low-grade ovarian carcinoma case with coincident LOH of PTCH1 and BRCA1, and a mutation in BRCA1.
abstract: We report a case of a 53-year-old woman with Grade 1 serous cystadenocarcinoma on her left ovary and metastatic serous adenocarcinoma on her right ovary. Serous carcinoma is the most common type of ovarian cancer, representing approximately half of all cases. Because of positive family history, the patient was referred for BRCA1/2 screening. Germline BRCA1 mutation c.676delT (p.C226VfsX8) was found, and in tumor tissue the normal allele was lost. Tumor tissue also had loss of heterozygosity in the PTCH1 gene, one of the major members of the Hedgehog-Gli (Hh-Gli) pathway. Gene expression analysis showed upregulation of the Hh-Gli pathway in both ovaries compared with healthy ovarian tissue. Primary cell culture was developed from the patient's tissue and showed downregulation of gene expression in response to cyclopamine, a Hh-Gli pathway inhibitor. The Hh-Gli signaling pathway may play a role in malignant transformation and metastasis of ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Zagreb University School of Medicine, Zagreb, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Maurac
authors.forename: Maja
authors.initials: M
authors.lastname: Sabol
authors.forename: Vesna
authors.initials: V
authors.lastname: Musani
authors.forename: Diana
authors.initials: D
authors.lastname: Car
authors.forename: Petar
authors.initials: P
authors.lastname: Ozretic
authors.forename: Drzislav
authors.initials: D
authors.lastname: Kalafatic
authors.forename: Slavko
authors.initials: S
authors.lastname: Oreskovic
authors.forename: Damir
authors.initials: D
authors.lastname: Babic
authors.forename: Sonja
authors.initials: S
authors.lastname: Levanat
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D002478:Cells, Cultured; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D014704:Veratrum Alkaloids; C000541:cyclopamine