OBJECTIVE A somatic mutational hotspot in the SF3B1 gene was reported in lactotroph tumours. The aim of our study was to examine the prevalence of driver SF3B1 variants in a multicentre independent cohort of patients with lactotroph tumours and correlate with clinical data. DESIGN AND METHODS This was a retrospective, multicentre study involving 282 patients with lactotroph tumours (including 6 metastatic lactotroph tumours) from 8 European centres. We screened SF3B1 exon 14 hotspot for somatic variants using Sanger sequencing and correlated with clinicopathological data. RESULTS We detected SF3B1 variants in seven patients with lactotroph tumours: c.1874G > A (p.Arg625His) (n = 4, 3 of which metastatic) and a previously undescribed in pituitary tumours variant c.1873C > T (p.Arg625Cys) (n = 3 aggressive pituitary tumours). In two metastatic lactotroph tumours with tissue available, the variant was detected in both primary tumour and metastasis. The overall prevalence of likely pathogenic SF3B1 variants in lactotroph tumours was 2.5%, but when we considered only metastatic cases, it reached the 50%. SF3B1 variants correlated with significantly larger tumour size; higher Ki67 proliferation index; multiple treatments, including radiotherapy and chemotherapy; increased disease-specific death; and shorter postoperative survival. CONCLUSIONS SF3B1 variants are uncommon in lactotroph tumours but may be frequent in metastatic lactotroph tumours. When present, they associate with aggressive tumour behaviour and worse clinical outcome.

中文翻译：

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泌乳素肿瘤中 SF3B1 变异的患病率和临床相关性。

目的 在泌乳素肿瘤中报道了 SF3B1 基因的体细胞突变热点。我们研究的目的是检查多中心独立的泌乳素瘤患者队列中驱动 SF3B1 变异的患病率，并与临床数据相关联。设计和方法 这是一项回顾性、多中心研究，涉及来自 8 个欧洲中心的 282 名泌乳素瘤患者（包括 6 例转移性泌乳素瘤）。我们使用 Sanger 测序筛选 SF3B1 外显子 14 热点的体细胞变异，并与临床病理数据相关。结果 我们在 7 名泌乳素肿瘤患者中检测到了 SF3B1 变异：c.1874G > A (p.Arg625His)（n = 4，其中 3 例为转移性）以及先前未在垂体瘤中描述的变异 c.1873C > T (p.Arg625Cys) （n = 3 例侵袭性垂体肿瘤）。在两个具有可用组织的转移性泌乳素肿瘤中，在原发肿瘤和转移肿瘤中均检测到了该变异。泌乳素肿瘤中可能致病的 SF3B1 变异的总体患病率为 2.5%，但当我们仅考虑转移性病例时，这一比例达到了 50%。SF3B1 变异与显着增大的肿瘤大小相关；Ki67增殖指数较高；多种治疗，包括放疗和化疗；特定疾病死亡人数增加；且术后生存期较短。结论 SF3B1 变异在泌乳素肿瘤中不常见，但在转移性泌乳素肿瘤中可能常见。当存在时，它们与侵袭性肿瘤行为和较差的临床结果相关。