title: Gorlin syndrome with an ovarian leiomyoma associated with a PTCH1 second hit.
abstract: We describe a Gorlin syndrome (GS) case with two different second hit mutations of PTCH1, one in a keratocystic odontogenic tumor (KCOT) and the other in an ovarian leiomyoma. GS is a rare genetic condition manifesting as multiple basal cell nevi associated with other features such as medulloblastomas, skeletal abnormalities, and ovarian fibromas. A 21-year-old Japanese woman with a history of two KCOTs was diagnosed with GS according to clinical criteria. A PTCH1 mutation, c.1427del T, was detected in peripheral blood. A novel PTCH1 mutation, c.264_265insAATA, had been found in the maxillary KCOT as a second hit mutation. More recently, the ovarian tumor was detected during a gynecological examination. Laparoscopic adnexectomy was performed, and the pathological diagnosis of the ovarian tumor was leiomyoma. Interestingly, another novel mutation, loss of heterozygosity spanning from 9q22.32 to 9q31.2, including PTCH1 and 89 other genes, was detected in this ovarian tumor, providing evidence of a second hit mutation. This is the first report describing a GS-associated ovarian tumor carrying a second hit in the PTCH1 region. We anticipate that accumulation of more cases will clarify the importance of second hit mutations in ovarian tumor formation in GS.
authors.affiliation: Department of Obstetrics and Gynecology, Tokyo Women's Medical University, Tokyo, Japan.|Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Yoshika
authors.initials: Y
authors.lastname: Akizawa
authors.affiliation: Department of Molecular Genetics, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyashita
authors.affiliation: Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Sasaki
authors.affiliation: Department of Obstetrics and Gynecology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Nagata
authors.affiliation: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Aoki
authors.affiliation: Department of Obstetrics and Gynecology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ishitani
authors.affiliation: Department of Surgical Pathology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.affiliation: Department of Obstetrics and Gynecology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Saito
mesh_terms: D001478:Basal Cell Nevus Syndrome / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000150:complications* / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D008279:Magnetic Resonance Imaging; D009154:Mutation; D010051:Ovarian Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D000072081:Patched-1 Receptor / Q000235:genetics*; D055815:Young Adult
chemical_list: D000072081:Patched-1 Receptor
keywords: Gorlin syndrome; LOH; PTCH1 second hit; leiomyoma; ovarian tumor