Identification of COL1A1/2 Mutations and Fusions With Noncoding RNA Genes in Bizarre Parosteal Osteochondromatous Proliferation (Nora Lesion)
(2023) In Modern Pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 36(2).- Abstract
Bizarre 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... (More)
Bizarre 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.
(Less)
- author
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- bizarre parosteal osteochondromatous proliferation, gene fusions, Nora lesion
- in
- Modern Pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
- volume
- 36
- issue
- 2
- article number
- 100011
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:36853784
- scopus:85149154480
- ISSN
- 1530-0285
- DOI
- 10.1016/j.modpat.2022.100011
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: Copyright © 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.
- id
- 29914e45-2f96-4041-9225-bf29f1fe0aad
- date added to LUP
- 2023-03-20 11:08:45
- date last changed
- 2024-09-20 09:49:50
@article{29914e45-2f96-4041-9225-bf29f1fe0aad, abstract = {{<p>Bizarre 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.</p>}}, author = {{Kao, Yu Chien and Yoshida, Akihiko and Hsieh, Tsung Han and Nord, Karolin H. and Saba, Karim H. and Ichikawa, Hitoshi and Tsai, Jen Wei and Huang, Hsuan Ying and Chih-Hsueh Chen, Paul and Fletcher, Christopher D.M. and Lee, Jen Chieh}}, issn = {{1530-0285}}, keywords = {{bizarre parosteal osteochondromatous proliferation; gene fusions; Nora lesion}}, language = {{eng}}, number = {{2}}, publisher = {{Nature Publishing Group}}, series = {{Modern Pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}}, title = {{Identification of COL1A1/2 Mutations and Fusions With Noncoding RNA Genes in Bizarre Parosteal Osteochondromatous Proliferation (Nora Lesion)}}, url = {{http://dx.doi.org/10.1016/j.modpat.2022.100011}}, doi = {{10.1016/j.modpat.2022.100011}}, volume = {{36}}, year = {{2023}}, }