Kao, Yu-ChienYu-ChienKaoYoshida, AkihikoAkihikoYoshidaHsieh, Tsung-HanTsung-HanHsiehNord, Karolin HKarolin HNordSaba, Karim HKarim HSabaIchikawa, HitoshiHitoshiIchikawaTsai, Jen-WeiJen-WeiTsaiHuang, Hsuan-YingHsuan-YingHuangChih-Hsueh Chen, PaulPaulChih-Hsueh ChenFletcher, Christopher D MChristopher D MFletcherJEN-CHIEH LEE2023-10-312023-10-312023-0208933952https://scholars.lib.ntu.edu.tw/handle/123456789/636701Bizarre parosteal osteochondromatous proliferation (BPOP) (Nora lesion) is a benign bone surface lesion, which most commonly occurs in the digits of young patients and has a high rate of recurrence. Histologically, it is composed of a mixture of disorganized bone, cartilage, and spindle cells in variable proportions and characterized by amorphous "blue bone" mineralization. Recurrent chromosomal abnormalities, including t(1;17)(q32-42;q21-23) and inv(7)(q21.1-22q31.3-32), have been reported in BPOP. However, the exact genes involved in the rearrangements remain unknown. In this study, we analyzed 8 BPOP cases affecting the fingers, toe, ulna, radius, and fibula of 5 female and 3 male patients, aged 5 to 68 years. RNA sequencing of 5 cases identified genetic fusions between COL1A2 and LINC-PINT in 3 cases and COL1A1::MIR29B2CHG fusion in 1, both validated using fluorescence in situ hybridization and reverse transcription (RT)-PCR. The remaining fusion-negative case harbored 3 COL1A1 mutations as revealed by whole-exome sequencing and confirmed using Sanger sequencing. All these genetic alterations were predicted to cause frameshift and/or truncation of COL1A1/2. The chromosomal locations of COL1A2 (7q21.3), LINC-PINT (7q32.3), COL1A1 (17q21.33), and MIR29B2CHG (1q32.2) were consistent with the breakpoints identified in the previous cytogenetic studies. Subsequent screening of 3 BPOPs using fluorescence in situ hybridization identified 1 additional case each with COL1A1 or COL1A2 rearrangement. Our findings are consistent with reported chromosomal abnormalities and implicate the disruption of type I collagen, and perhaps of either noncoding RNA gene as a tumor suppressor, in the tumorigenesis of BPOP. The prevalence and tumorigenic mechanisms of these COL1A1/2 alterations in BPOP require further investigation.enNora lesion; bizarre parosteal osteochondromatous proliferation; gene fusions[SDGs]SDG3journal article10.1016/j.modpat.2022.100011368537842-s2.0-85149154480https://api.elsevier.com/content/abstract/scopus_id/85149154480