OBJECTIVE: To investigate HRPT2 in jaw ossifying fibroma (OF), fibrous dysplasia (FD), and osteosarcoma (OS). STUDY DESIGN: We combined microsatellite loss of heterozygosity (LOH), HRPT2 sequence alterations at the mRNA level by reverse-transcription polymerase chain reaction (PCR), cDNA sequencing, and quantitative PCR (qPCR) and immunohistochemistry (IHC) in a total of 19 OF, 15 FD, and 9 OS. Because HRPT2 (parafibromin) interacts with cyclin D1, we investigated cyclin D1 expression with the use of qPCR and IHC. RESULTS: LOH was detected in 3/5 FD, 6/9 OF, and 2/2 OS heterozygous samples. LOH was not associated with decreased mRNA levels or HRPT2 protein expression except for 1 OF which harbored an inactivating mutation. However, this tumor did not display altered transcription or protein levels of HRPT2 nor cyclin compared with the other OF. CONCLUSIONS: The contribution of HRPT2 inactivation to the pathogenesis of OF, FD, and OS is marginal at best and may be limited to progression rather than tumor initiation.
OBJECTIVE: To investigate HRPT2 in jaw ossifying fibroma (OF), fibrous dysplasia (FD), and osteosarcoma (OS). STUDY DESIGN: We combined microsatellite loss of heterozygosity (LOH), HRPT2 sequence alterations at the mRNA level by reverse-transcription polymerase chain reaction (PCR), cDNA sequencing, and quantitative PCR (qPCR) and immunohistochemistry (IHC) in a total of 19 OF, 15 FD, and 9 OS. Because HRPT2 (parafibromin) interacts with cyclin D1, we investigated cyclin D1 expression with the use of qPCR and IHC. RESULTS: LOH was detected in 3/5 FD, 6/9 OF, and 2/2 OS heterozygous samples. LOH was not associated with decreased mRNA levels or HRPT2 protein expression except for 1 OF which harbored an inactivating mutation. However, this tumor did not display altered transcription or protein levels of HRPT2 nor cyclin compared with the other OF. CONCLUSIONS: The contribution of HRPT2 inactivation to the pathogenesis of OF, FD, and OS is marginal at best and may be limited to progression rather than tumor initiation.
Authors: Jessica Costa-Guda; Chetanya Pandya; Maya Strahl; Patricia Taik; Robert Sebra; Rong Chen; Andrew V Uzilov; Andrew Arnold Journal: J Endocr Soc Date: 2021-05-08