Abstract：
BACKGROUND: Cellular angiofibroma, a rare benign mesenchymal neoplasm, is classified within the 13q/RB1 family of tumors due to morphological, immunohistochemical, and genetic similarities with spindle cell lipoma. Here, genetic data reveal pathogenetic heterogeneity in cellular angiofibroma.
METHODS: Three cellular angiofibromas were studied using G-banding/Karyotyping, array comparative genomic hybridization, RNA sequencing, and direct cycling sequencing.
RESULTS: The first tumor carried a del(13)(q12) together with heterozygous loss and minimal expression of the RB1 gene. Tumors two and three displayed chromosome 8 abnormalities associated with chimeras of the pleomorphic adenoma gene 1 (PLAG1). In tumor 2, the cathepsin B (CTSB) fused to PLAG1 (CTSB::PLAG1) while in tumor 3, the mir-99a-let-7c cluster host gene (MIR99AHG) fused to PLAG1 (MIR99AHG::PLAG1), both leading to elevated expression of PLAG1 and insulin growth factor 2.
CONCLUSIONS: This study uncovers two genetic pathways contributing to the pathogenetic heterogeneity within cellular angiofibromas. The first aligns with the 13q/RB1 family of tumors and the second involves PLAG1-chimeras. These findings highlight the diverse genetic landscape of cellular angiofibromas, providing insights into potential diagnostic strategies.
METHODS: Three cellular angiofibromas were studied using G-banding/Karyotyping, array comparative genomic hybridization, RNA sequencing, and direct cycling sequencing.
RESULTS: The first tumor carried a del(13)(q12) together with heterozygous loss and minimal expression of the RB1 gene. Tumors two and three displayed chromosome 8 abnormalities associated with chimeras of the pleomorphic adenoma gene 1 (PLAG1). In tumor 2, the cathepsin B (CTSB) fused to PLAG1 (CTSB::PLAG1) while in tumor 3, the mir-99a-let-7c cluster host gene (MIR99AHG) fused to PLAG1 (MIR99AHG::PLAG1), both leading to elevated expression of PLAG1 and insulin growth factor 2.
CONCLUSIONS: This study uncovers two genetic pathways contributing to the pathogenetic heterogeneity within cellular angiofibromas. The first aligns with the 13q/RB1 family of tumors and the second involves PLAG1-chimeras. These findings highlight the diverse genetic landscape of cellular angiofibromas, providing insights into potential diagnostic strategies.
摘要：
背景：细胞性血管纤维瘤，一种罕见的良性间质瘤,由于形态学原因，被分类在13q/RB1肿瘤家族中，免疫组织化学，与梭形细胞脂肪瘤的遗传相似性。这里,遗传数据揭示了细胞性血管纤维瘤的发病异质性。
方法：使用G显带/核型分析研究了三种细胞性血管纤维瘤，阵列比较基因组杂交,RNA测序，和直接循环测序。
结果：第一个肿瘤带有del（13）（q12），杂合缺失和RB1基因的最小表达。肿瘤2和3显示与多形性腺瘤基因1（PLAG1）的嵌合体相关的8号染色体异常。在肿瘤2中，组织蛋白酶B（CTSB）与PLAG1（CTSB：：PLAG1）融合，而在肿瘤3中，mir-99a-let-7c簇宿主基因（MIR99AHG）与PLAG1（MIR99AHG：：PLAG1）融合，两者均导致PLAG1和胰岛素生长因子2的表达升高。
结论：本研究揭示了导致细胞血管纤维瘤发病异质性的两条遗传途径。第一个与肿瘤的13q/RB1家族对齐，第二个涉及PLAG1-嵌合体。这些发现突出了细胞血管纤维瘤的不同遗传景观，提供潜在诊断策略的见解。
方法：使用G显带/核型分析研究了三种细胞性血管纤维瘤，阵列比较基因组杂交,RNA测序，和直接循环测序。
结果：第一个肿瘤带有del（13）（q12），杂合缺失和RB1基因的最小表达。肿瘤2和3显示与多形性腺瘤基因1（PLAG1）的嵌合体相关的8号染色体异常。在肿瘤2中，组织蛋白酶B（CTSB）与PLAG1（CTSB：：PLAG1）融合，而在肿瘤3中，mir-99a-let-7c簇宿主基因（MIR99AHG）与PLAG1（MIR99AHG：：PLAG1）融合，两者均导致PLAG1和胰岛素生长因子2的表达升高。
结论：本研究揭示了导致细胞血管纤维瘤发病异质性的两条遗传途径。第一个与肿瘤的13q/RB1家族对齐，第二个涉及PLAG1-嵌合体。这些发现突出了细胞血管纤维瘤的不同遗传景观，提供潜在诊断策略的见解。
