Discovery of Novel TULP4/ACTN4/EWSR1/ACTB::MYB and ESRRG::DNM3 Fusions Expands Molecular Landscape of Adenoid Cystic Carcinoma Beyond Fusions Between MYB/MYBL1 and NFIB Genes.

IF 4.5 1区 医学 Q1 PATHOLOGY American Journal of Surgical Pathology Pub Date : 2024-09-04 DOI:10.1097/PAS.0000000000002304
Alena Skálová, Natálie Klubíčková, Martina Bradová, Abbas Agaimy, Niels J Rupp, Ivan Damjanov, Georgina Kolnikova, Petr Martínek, Petr Šteiner, Petr Grossmann, Tomas Vaněček, Michal Michal, Ilmo Leivo
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Abstract

Adenoid cystic carcinoma (AdCC) is one of the most common salivary gland malignancies and occurs in all major and minor salivary gland and seromucous gland sites. AdCCs of salivary gland origin have long been categorized as fusion-defined carcinomas owing to the almost consistent presence of fusion genes MYB::NFIB, or less commonly MYBL1::NFIB. We collected a cohort of 95 cases of AdCC, which were largely characterized by canonical fusions MYB::NFIB (49 cases) or MYBL1::NFIB (9 cases). In additional 11 cases of AdCC, rearrangements in MYB or NFIB genes were detected by FISH. In addition, NGS revealed novel noncanonical fusion transcripts EWSR1::MYB; ACTB::MYB; ESRRG::DNM3, MYB::TULP4, and ACTN4::MYB, each of them in 1 case. The tumors that showed noncanonical fusions had features of metatypical AdCC with a diverse architecture, lobulated multinodular growth pattern, and hypercellular peripheral palisading of nuclei (2 cases), tubular hypereosinophilia (2 cases), and pale eosinophilic to vacuolated (bubbly) cytoplasm (3 cases). Our study documented 3 cases of AdCC of salivary glands harboring novel gene fusions TULP4::MYB, ACTN4::MYB, and ACTB::MYB, in 1 case each, which have not been described before. A rare EWSR1::MYB fusion was detected in 1 case. Moreover, 1 case of sinonasal metatypical AdCC showed EWSR1 rearrangement detected by FISH. Also, 1 case with an ESRRG::DNM3 fusion of unknown significance is described in this study. These discoveries illustrate how broad molecular profiling will expand understanding of changes in known entities.

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新型 TULP4/ACTN4/EWSR1/ACTB::MYB 和 ESRRG::DNM3 融合的发现扩展了腺样囊性癌的分子图谱,超越了 MYB/MYBL1 和 NFIB 基因之间的融合。
腺样囊性癌(AdCC)是最常见的唾液腺恶性肿瘤之一,可发生于所有主要和次要唾液腺及血清粘液腺部位。长期以来,唾液腺来源的腺囊肿一直被归类为融合定义的癌,因为几乎一致存在融合基因 MYB::NFIB,或较少见的 MYBL1::NFIB。我们共收集了 95 例 AdCC,这些病例的主要特征是典型融合 MYB::NFIB (49 例)或 MYBL1::NFIB (9 例)。在另外 11 例 AdCC 中,通过 FISH 检测到了 MYB 或 NFIB 基因的重排。此外,NGS 还发现了新型非典型融合转录本 EWSR1::MYB、ACTB::MYB、ESRRG::DNM3、MYB::TULP4 和 ACTN4::MYB,各 1 例。出现非典型融合的肿瘤具有元典型 AdCC 的特征,包括多样化的结构、分叶状多结节生长模式、细胞核周边钙化(2 例)、管状嗜酸性细胞增多(2 例)和淡嗜酸性至空泡状(气泡状)胞质(3 例)。我们的研究记录了 3 例唾液腺 AdCC 病例,其中 1 例携带新型基因融合 TULP4::MYB、ACTN4::MYB 和 ACTB::MYB,这些基因融合以前从未报道过。有 1 例检测到罕见的 EWSR1::MYB 融合。此外,1 例鼻窦偏典型 AdCC 病例通过 FISH 检测到 EWSR1 重排。本研究还描述了1例意义不明的ESRRG::DNM3融合病例。这些发现说明了广泛的分子图谱分析将如何扩展对已知实体变化的理解。
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来源期刊
CiteScore
10.30
自引率
5.40%
发文量
295
审稿时长
1 months
期刊介绍: The American Journal of Surgical Pathology has achieved worldwide recognition for its outstanding coverage of the state of the art in human surgical pathology. In each monthly issue, experts present original articles, review articles, detailed case reports, and special features, enhanced by superb illustrations. Coverage encompasses technical methods, diagnostic aids, and frozen-section diagnosis, in addition to detailed pathologic studies of a wide range of disease entities. Official Journal of The Arthur Purdy Stout Society of Surgical Pathologists and The Gastrointestinal Pathology Society.
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