美韓等國科學家7月1日發(fā)表研究報告稱,，某個基因的突變可能是正常細胞轉(zhuǎn)變成癌細胞的最早征兆。這一發(fā)現(xiàn)將有助于早期發(fā)現(xiàn)和及時治療癌癥。
癌細胞由正常細胞“異化”而來，在此過程中發(fā)生一系列基因突變。有些突變遠在正常細胞癌化之前就已發(fā)生,，這些最早突變的基因，可能成為癌癥早期診斷的“風向標”,。研究人員必須根據(jù)癌細胞現(xiàn)有基因序列確定基因的突變時間,，這一工作相當于基因研究中的“考古學”。
美國加州大學舊金山分校和伯克利分校,、俄勒岡衛(wèi)生科學大學及韓國三星先進技術研究所等機構的研究人員在最新一期《癌癥發(fā)現(xiàn)》期刊上報告說,，他們對兩種原發(fā)性癌細胞的TP53基因分析表明，在多數(shù)情況下,，這個基因的突變是在細胞癌化之前最早發(fā)生的,，而不是原先所認為的那樣在癌化后發(fā)生。
研究人員分析了常見皮膚癌——鱗狀細胞瘤和常見卵巢癌——漿液性卵巢腺瘤中癌細胞的基因突變過程后發(fā)現(xiàn),，TP53基因的序列早在細胞癌化之前就已異常復制,。TP53是已知的致癌基因，與這兩種癌癥密切相關,。
研究人員指出,，雖然癌癥與許多基因突變有關，但最早的基因突變很可能是后來進一步異常的前奏,。癌癥的診斷和治療越早越好,，因此確定癌細胞基因突變的時間順序，找出細胞癌化的“風向標”,，將極大幫助人們早期發(fā)現(xiàn)和治療癌癥,。（生物谷Bioon.com）
生物谷推薦原文出處：
Cancer Discovery doi: 10.1158/2159-8290.CD-11-0028
Temporal Dissection of Tumorigenesis in Primary Cancers
Steffen Durinck, Christine Ho, Nicholas J. Wang, Wilson Liao, Lakshmi R. Jakkula1, Eric A. Collisson, Jennifer Pons, Sai-Wing Chan, Ernest T. Lam, Catherine Chu, Kyunghee Park, Sung-woo Hong, Joe S. Hur, Nam Huh, Isaac M. Neuhaus, Siegrid S. Yu, Roy C. Grekin, Theodora M. Mauro, James E. Cleaver, Pui-Yan Kwok, Philip E. LeBoit, Gad Getz, Kristian Cibulskis, Jon C. Aster, Haiyan Huang, Elizabeth Purdom, Jian Li, Lars Bolund, Sarah T. Arron, Joe W. Gray, Paul T. Spellman and Raymond J. Cho
Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing of tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations in a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence and copy number information to reconstruct the order of abnormalities as individual tumors evolve for 2 separate cancer types. We detect vast, unreported expansion of simple mutations sharply demarcated by recombinative loss of the second copy of TP53 in cutaneous squamous cell carcinomas (cSCC) and serous ovarian adenocarcinomas, in the former surpassing 50 mutations per megabase. In cSCCs, we also report diverse secondary mutations in known and novel oncogenic pathways, illustrating how such expanded mutagenesis directly promotes malignant progression. These results reframe paradigms in which TP53 mutation is required later, to bypass senescence induced by driver oncogenes.
Significance: Our approach reveals sequential ordering of oncogenic events in individual cancers, based on chromosomal rearrangements. Identifying the earliest abnormalities in cancer represents a critical step in timely diagnosis and deployment of targeted therapeutics.
