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.
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。