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.

Non-canonical Hedgehog signaling activation in ovarian borderline tumors and ovarian carcinomas

“…RNA was reversetranscribed using TaqMan Reverse Transcription Reagents (Applied Biosystems), and qRT-PCR was performed on a CFX96 machine (Bio-Rad) using EVAGreen dye (Bio-Rad). Primers and conditions used were described previously (33,34). expression levels for each gene were first calculated as ∆Ct relative to the housekeeping gene RPLP0.…”

“…Cell culture experiments. Primary culture was established from a high-grade ovarian tumor sample (FIGO IIIC) as previously described (33) and maintained in DMEM+10%FBS, as was the human ovarian adenocarcinoma cell line SKOV-3. Both cultures were mycoplasma-free.…”

Combination of Cyclopamine and Tamoxifen Promotes Survival and Migration of MCF-7 Breast Cancer Cells – Interaction of Hedgehog-Gli and Estrogen Receptor Signaling Pathways

“…RNA extraction and qRT-PCR were performed as previously described [24] , with primers ERα F 5′-CAGATGGTCAGTGCCTTGTTGG-3′ , R 5′-CCAAGAGCAAGTTAGGAGCAAACAG-3′ [25] and RPLP0 , PTCH1 and GLI1 [26] , [27] . Expression was normalized using RPLP0 housekeeping gene and relative fold change was calculated using the 2 −ΔΔCt formula.…”