泪道器官的恶性肿瘤罕见且预后常较差，目前尚无明确的治疗标准。目前对这些罕见肿瘤的遗传基因组特性了解还较少，因此治疗通常遵循其常见的唾液腺肿瘤标准。为了更清楚地阐明其病理生理学并发现潜在的治疗靶点，我们研究了八例泪道器官肿瘤的遗传基因组特性。通过DNA和RNA测序来鉴定遗传突变和基因融合。通过免疫组化、荧光原位杂交和逆转录聚合酶链反应结合Sanger测序来确认已鉴定的分子改变。在六例肿瘤中检测到遗传改变。在五例腺样囊性癌（ACC）中，有四例MYB或MYBL1基因的突变已得到证实，包括MYB::NFIB融合，MYBL1::NFIB融合，MYB扩增和一个新的NFIB::THSD7B融合。在ACC中还鉴定到编码表观遗传修饰因子的基因突变，以及NOTCH1、FGFR2和ATM突变。一个由错构瘤癌变而来的癌瘤显示了TP53和CIC突变以及ERBB2扩增。一个过渡细胞癌与HPV16感染相关。一个未明确指定的腺癌未发现遗传改变。我们的研究突显了与泪道系统肿瘤相关的多种分子改变，强调了在这些肿瘤中进行分子检测的重要性，这可以揭示潜在的靶向突变。我们的结果也支持一个共同生理病理学假设，即无论其原发位置如何，所有ACC的发生机制是相同的。© 2023 John Wiley & Sons Ltd.

Malignant tumours of the lacrimal apparatus are rare and frequently show a poor prognosis, with no clear therapeutic standards. Characterisation of the genetic landscape of these rare tumours is sparse, and therefore therapeutics generally follow those of their common salivary gland counterparts. To further clarify the pathophysiology and discover potential therapeutic targets, we investigated the genetic landscape of eight tumours of the lacrimal apparatus.DNA and RNA sequencing were performed to identify genetic mutations and gene fusions. Immunohistochemistry, fluorescence in-situ hybridisation and reverse transcription-polymerase chain reaction followed by Sanger sequencing were performed to confirm the identified molecular alterations. Genetic alterations were detected in six tumours. Among five adenoid cystic carcinomas (ACC), four had confirmed alterations of MYB or MYBL1 genes, including a MYB::NFIB fusion, a MYBL1::NFIB fusion, a MYB amplification and a novel NFIB::THSD7B fusion. Mutations in genes encoding epigenetic modifiers, as well as NOTCH1, FGFR2 and ATM mutations, were also identified in ACCs. A carcinoma ex pleomorphic adenoma showed TP53 and CIC mutations and an amplification of ERBB2. A transitional cell carcinoma was associated with HPV16 infection. No genetic alteration was found for one adenocarcinoma, not otherwise specified.Our study highlights the variety of molecular alterations associated with lacrimal system tumours and emphasises the importance of molecular testing in these tumours, which can reveal potentially targetable mutations. Our results also reinforce the hypothesis of a common physiopathology of all ACCs, regardless of their primary location.© 2023 John Wiley & Sons Ltd.