Identification of a novel somatic mutation of POU6F2 by whole-genome sequencing in prolactinoma
Identification of a novel somatic mutation of POU6F2 by whole-genome sequencing in prolactinoma
复制标题
通过全基因组测序鉴定泌乳素瘤中 POU6F2 的新型体细胞突变
DOI：
10.1002/mgg3.1022
复制
发表时间：
2019-11-06
影响因子：
2
通讯作者：
Zhang, Yazhuo
中科院分区：
文献类型：
--
作者：
Miao, Yazhou;Li, Chuzhong;Zhang, Yazhuo
垂体腺瘤是最常见的颅内肿瘤之一，大约一半的垂体腺瘤是分泌催乳素（PRL）的垂体腺瘤。泌乳素瘤中普遍存在的遗传改变尚不清楚。方法：我们报告一个极度侵袭性的巨大泌乳素瘤伴周围骨质严重破坏的病例。该患者表现出对多巴胺能药物的耐药性。通过全基因组测序，我们鉴定了POU 6 F2基因中的两个新的体细胞突变（NM_001166018.2：c. 839 C>T; NM_001166018.2：c. 875A>G）。结果本报告是第一个确定这些体细胞突变的POU 6 F2基因催乳素瘤。我们发现这两个突变明显降低了POU 6 F2的表达水平。抑制POU 6 F2活性可增加大鼠垂体细胞的增殖和PRL分泌，但POU 6 F2过表达的细胞增殖和PRL分泌减少。结论POU 6 F2可能在泌乳素腺瘤的发生发展中起重要作用，并可能成为开发新的治疗泌乳素腺瘤的靶点。
Background Pituitary adenomas (PAs) are one of the most common intracranial tumors; approximately half of PAs are prolactin (PRL)-secreting PAs (prolactinomas). The genetic alterations prevalent in prolactinomas are unknown. Methods Here, we present a patient with an extremely aggressive and giant prolactinoma accompanied by serious destruction of the surrounding bone mass. This patient exhibited resistance to dopaminergic drugs. Through whole-genome sequencing, we identified two novel somatic mutations in the POU6F2 gene (NM_001166018.2: c. 839 C>T; NM_001166018.2: c. 875A>G). Results This report is the first to identify these somatic mutations in the POU6F2 gene in a prolactinoma. We found that these two mutations obviously decreased the expression level of POU6F2. Inhibition of POU6F2 activity increased the cell proliferation and PRL secretion in rat pituitary cells, but proliferation and PRL secretion were decreased in cells with POU6F2 overexpression. Conclusions POU6F2 might play a crucial role in the development of prolactinomas and may be a promising target for developing new therapies against prolactinomas.