Genetic Heterogeneity in Cellular Angiofibromas

IF 3.1 2区医学 Q2 GENETICS & HEREDITY

Genes, Chromosomes & Cancer Pub Date : 2024-08-09 DOI:10.1002/gcc.23262

Ioannis Panagopoulos, Kristin Andersen, Ingvild Lobmaier, Marius Lund-Iversen

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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.

Conclusion

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.

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细胞性血管纤维瘤的遗传异质性

背景：细胞性血管纤维瘤是一种罕见的良性间质肿瘤，由于在形态学、免疫组化和遗传学方面与纺锤形细胞脂肪瘤相似，因此被归类为13q/RB1家族肿瘤。遗传学数据揭示了细胞性血管纤维瘤的致病异质性：方法：使用 G 带/核型分析、阵列比较基因组杂交、RNA 测序和直接循环测序对三个细胞性血管纤维瘤进行了研究：第一个肿瘤带有 del(13)(q12)，同时伴有 RB1 基因的杂合性缺失和极少表达。第二和第三个肿瘤显示与多形性腺瘤基因1（PLAG1）嵌合体相关的8号染色体异常。在肿瘤二中，溶血蛋白酶 B（CTSB）与 PLAG1 融合（CTSB::PLAG1），而在肿瘤三中，mir-99a-let-7c 簇宿主基因（MIR99AHG）与 PLAG1 融合（MIR99AHG::PLAG1），两者均导致 PLAG1 和胰岛素生长因子 2 的表达升高：本研究发现了导致细胞性血管纤维瘤发病异质性的两条遗传途径。结论：这项研究发现了两种导致细胞性血管纤维瘤发病异质性的遗传途径，第一种与 13q/RB1 肿瘤家族相一致，第二种涉及 PLAG1-嵌合体。这些发现凸显了细胞性血管纤维瘤的遗传多样性，为潜在的诊断策略提供了启示。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genes, Chromosomes & Cancer 医学-遗传学

CiteScore

7.00

自引率

8.10%

发文量

审稿时长

4-8 weeks

期刊介绍： Genes, Chromosomes & Cancer will offer rapid publication of original full-length research articles, perspectives, reviews and letters to the editors on genetic analysis as related to the study of neoplasia. The main scope of the journal is to communicate new insights into the etiology and/or pathogenesis of neoplasia, as well as molecular and cellular findings of relevance for the management of cancer patients. While preference will be given to research utilizing analytical and functional approaches, descriptive studies and case reports will also be welcomed when they offer insights regarding basic biological mechanisms or the clinical management of neoplastic disorders.