文章：

垂体神经内分泌肿瘤体细胞遗传变异热点研究

Hotspots of Somatic Genetic Variation in Pituitary Neuroendocrine Tumors

原文发布日期：1 December 2023

DOI: 10.3390/cancers15235685

类型: Article

开放获取: 是

英文摘要：

The most common genetic drivers of pituitary neuroendocrine tumors (PitNETs) lie within mutational hotspots, which are genomic regions where variants tend to cluster. Some of these hotspot defects are unique to PitNETs, while others are associated with additional neoplasms. Hotspot variants inGNASandUSP8are the most common genetic causes of acromegaly and Cushing’s disease, respectively. Although it has been proposed that these genetic defects could define specific clinical phenotypes, results are highly variable among studies. In contrast,DICER1hotspot variants are associated with a familial syndrome of cancer predisposition, and only exceptionally occur as somatic changes. A small number of non-USP8-driven corticotropinomas are due to somatic hotspot variants inUSP48orBRAF; the latter is a well-known mutational hotspot in cancer. Finally, somatic variants affecting a hotspot inSF3B1have been associated with multiple cancers and, more recently, with prolactinomas. Since the associations ofBRAF,USP48, andSF3B1hotspot variants with PitNETs are very recent, their effects on clinical phenotypes are still unknown. Further research is required to fully define the role of these genetic defects as disease biomarkers and therapeutic targets.

摘要翻译： 

垂体神经内分泌肿瘤（PitNETs）最常见的遗传驱动因素位于突变热点区域，即基因组中变异倾向于聚集的区域。其中部分热点缺陷为PitNETs所特有，而另一些则与其他肿瘤相关。GNAS和USP8的热点变异分别是肢端肥大症和库欣病最常见的遗传病因。尽管有观点认为这些遗传缺陷可能界定特定的临床表型，但不同研究的结果差异显著。相比之下，DICER1热点变异与家族性癌症易感综合征相关，仅极少数情况下作为体细胞变异出现。少数非USP8驱动的促肾上腺皮质激素腺瘤由USP48或BRAF的体细胞热点变异引起；后者是癌症中众所周知的突变热点。最后，影响SF3B1热点的体细胞变异与多种癌症相关，最近还被发现与泌乳素瘤存在关联。由于BRAF、USP48和SF3B1热点变异与PitNETs的关联性发现较晚，其对临床表型的影响尚不明确。需要进一步研究以全面界定这些遗传缺陷作为疾病生物标志物和治疗靶点的作用。

原文链接：

Hotspots of Somatic Genetic Variation in Pituitary Neuroendocrine Tumors