Nature Genetics:RABL3突变可作为遗传性胰腺癌的基因检测靶点

2019-09-23 MedSci MedSci原创

胰管腺癌是一种侵袭性肿瘤,治疗方法有限。大约10%的病例表现为家族倾向性,但多数家庭的致病基因并不明确。研究人员通过全外显子测序对一个有多位胰管腺癌患者的家族进行分析,在RAS致癌家族样3(RABL3)基因上发现一个生殖系截短突变。rabl3杂合突变型斑马鱼表现为发生癌症的易感性增强。转录组学和质朴分析显示RABL3参与RAS通路的调控,并与调节RAS GTPases 异戊烯化的伴侣蛋白RAP1G

胰管腺癌是一种侵袭性肿瘤,治疗方法有限。大约10%的病例表现为家族倾向性,但多数家庭的致病基因并不明确。

研究人员通过全外显子测序对一个有多位胰管腺癌患者的家族进行分析,在RAS致癌家族样3(RABL3)基因上发现一个生殖系截短突变。

rabl3杂合突变型斑马鱼表现为发生癌症的易感性增强。转录组学和质朴分析显示RABL3参与RAS通路的调控,并与调节RAS GTPases 异戊烯化的伴侣蛋白RAP1GDS1 (SmgGDS)相互作用。

截短突变型RABL3蛋白可加速KRAS的异戊烯化,需要RAS蛋白来促进细胞增殖。最后,发育障碍患者群体的证据表明,RASopathy综合征中存在也存在生殖系RABL3突变。

本研究表明RABL3突变可作为癌症家族基因检测的一个靶点,并揭示了RAS活性在发育和癌症中失调的分子机制。

原始出处:

Sahar Nissim, et al.Mutations in RABL3 alter KRAS prenylation and are associated with hereditary pancreatic cancer.Nature Genetics. 12 August, 2019. 51, pages1308–1314

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    2020-06-19 liye789132251
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    2019-12-22 cy0324
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    2020-04-17 canlab
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    2020-02-01 huperzia
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