近日,，刊登在國際著名雜志Nature Genetics上的一項研究表明，胚胎期機體的遺傳組成（基因組成）或許會引發(fā)成年后腫瘤的出現,。一個細胞可以分裂為兩個具有相同特征,、相同遺傳物質的細胞之后；基因中的遺傳突變會在胚胎發(fā)育的過程中發(fā)生,，而且在細胞分裂的過程中,，這種突變會被傳遞到子代細胞中，結果一個個體中細胞會發(fā)生不同的遺傳突變,，這種現象被成為鑲嵌現象,，與很多癌癥直接相關，但是目前科學界對于這種遺傳突變的信息知之甚少,。
研究者對于67個皮膚具有先天性損傷可以發(fā)展至腫瘤的病人（NS）進行了詳盡的遺傳學研究,，同時研究者研究了席梅耳潘寧格綜合征（SS），這些病人中大腦和眼睛都受到了嚴重影響,。研究者在這些病人損害部位的活組織檢測中首次發(fā)現了RAS家族基因的突變（在NS中為97%,；SS中為100%），RAS家族蛋白在細胞分裂調節(jié)中扮演著主要角色,。通過分析無損害組織研究者發(fā)現這些組織的基因序列均正常,。后期研究中，凡事基因家族發(fā)生鑲嵌現象的病人都會發(fā)展形成腫瘤,。
上述的研究結果以及前期的結果揭示出,，在胚胎發(fā)育階段,，如果機體基因發(fā)生突變將會很容易誘發(fā)成年后腫瘤的形成。
57,，000個人的基因組學分析
一項對于57,，000個個體的完整基因組學分析數據揭示，遠距離起源的鑲嵌現象在腫瘤病人中相比無癌癥個體中廣泛存在,。從基因組學分析可知,，相同個體的細胞遺傳組成也存在差異可變性，因此某些突變意味著癌癥風險的增加,，因此特定的病人必須經常去檢查看看是否其機體損害仍然在繼續(xù)進行下去,。（生物谷Bioon.com）
編譯自：Mosaicism in Cancer: Genetic Makeup of Embryo May Cause Appearance of Tumors in Adult Life
編譯者：T.Shen
doi:10.1038/ng.2316
PMC:
PMID:
Postzygotic HRAS and KRAS mutations cause nevus sebaceous and Schimmelpenning syndrome
Leopold Groesser,1 Eva Herschberger,1 Arno Ruetten,2 Claudia Ruivenkamp,3 Enrico Lopriore,4 Markus Zutt,5 Thomas Langmann,6, 7 Sebastian Singer,1 Laura Klingseisen,8 Wulf Schneider-Brachert,8 Agusti Toll,9 Francisco X Real,10, 11 Michael Landthaler1 & Christian Hafner1
Nevus sebaceous is a common congenital cutaneous malformation. Affected individuals may develop benign and malignant secondary tumors in the nevi during life. Schimmelpenning syndrome is characterized by the association of nevus sebaceous with extracutaneous abnormalities. We report that of 65 sebaceous nevi studied, 62 (95%) had mutations in the HRAS gene and 3 (5%) had mutations in the KRAS gene. The HRAS c.37G>C mutation, which results in a p.Gly13Arg substitution, was present in 91% of lesions. Nonlesional tissues from 18 individuals had a wild-type sequence, confirming genetic mosaicism. The HRAS c.37G>C mutation was also found in 8 of 8 associated secondary tumors. Mosaicism for HRAS c.37G>C and KRAS c.35G>A mutations was found in two individuals with Schimmelpenning syndrome. Functional analysis of HRAS c.37G>C mutant cells showed constitutive activation of the MAPK and PI3K-Akt signaling pathways. Our results indicate that nevus sebaceous and Schimmelpenning syndrome are caused by postzygotic HRAS and KRAS mutations. These mutations may predispose individuals to the development of secondary tumors in nevus sebaceous.
