Science：科學家發(fā)現(xiàn)肺癌或許可以隱藏20年之久

發(fā)稿時間：2015-08-06來源：圣谷同創(chuàng)

近日，刊登在國際雜志Science上 的一篇研究論文中，來自英國癌癥研究中心的研究人員通過研究發(fā)現(xiàn)，肺癌在轉(zhuǎn)化成為惡性之前可以在人類機體中潛伏長達20年之久；文章中研究人員對7位肺癌 病人進行研究，包括吸煙者、已戒煙者及從不吸煙的個體，結(jié)果發(fā)現(xiàn)，在機體中發(fā)生第一次促發(fā)癌癥的遺傳突變后，該突變會在機體中隱藏很多年直到新發(fā)突變產(chǎn) 生，最終這些突變會聯(lián)合起來引發(fā)疾病的惡化。
??Charles Swanton教授表示，盡管針對肺癌有很多靶向性的療法，但是肺癌患者的生存率依然很低，通過揭示肺癌的發(fā)病原因或許就可以為我們后期開發(fā)治療肺癌的新型療法提供一定的幫助。
??文章中研究人員闡明了吸煙在引發(fā)肺癌過程中的重要作用，研究者表示，許多早期的遺傳突變都是由于吸煙引發(fā)的，但是隨著疾病發(fā)生這些突變就會變得不再占據(jù)主導地位，而隨之而來的將是由蛋白質(zhì)APOBEC控制產(chǎn)生的腫瘤突變。
??在肺癌患者機體中發(fā)現(xiàn)的多種遺傳突變就可以幫助解釋靶向療法為何屢屢受挫，每年大約有4 萬人會患上肺癌，研究者Nic Jones指出，目前的研究急需我們開發(fā)出肺癌的早期診斷技術(shù)來幫助預(yù)防和阻斷肺癌的惡化，如果在疾病發(fā)生的萌芽階段就將其扼殺住，那么患者治愈的希望非 常之大。（轉(zhuǎn)化醫(yī)學網(wǎng)360zhyx.com）
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轉(zhuǎn)化醫(yī)學網(wǎng)推薦的原文摘要：

Spatial and temporal diversity in genomic instability processes defines lung cancer evolution
Science   DOI: 10.1126/science.1253462
Elza C. de Bruin1,*, Nicholas McGranahan2,3,*, Richard Mitter2,*, Max Salm2,*, David C. Wedge4,*, Lucy Yates4,5,?, Mariam Jamal-Hanjani1,?, Seema Shafi1, Nirupa Murugaesu1, Andrew J. Rowan2, Eva Gr?nroos2, Madiha A. Muhammad1, Stuart Horswell2, Marco Gerlinger2, Ignacio Varela6, David Jones4, John Marshall4, Thierry Voet4,7, Peter Van Loo4,7, Doris M. Rassl8, Robert C. Rintoul8, Sam M. Janes9, Siow-Ming Lee1,10, Martin Forster1,10, Tanya Ahmad10, David Lawrence10, Mary Falzon10, Arrigo Capitanio10, Timothy T. Harkins11, Clarence C. Lee11, Warren Tom11, Enock Teefe11, Shann-Ching Chen11, Sharmin Begum2, Adam Rabinowitz2, Benjamin Phillimore2, Bradley Spencer-Dene2, Gordon Stamp2, Zoltan Szallasi12,13, Nik Matthews2, Aengus Stewart2, Peter Campbell4, Charles Swanton1,2,?
Spatial and temporal dissection of the genomic changes occurring during the evolution of human non–small cell lung cancer (NSCLC) may help elucidate the basis for its dismal prognosis. We sequenced 25 spatially distinct regions from seven operable NSCLCs and found evidence of branched evolution, with driver mutations arising before and after subclonal diversification. There was pronounced intratumor heterogeneity in copy number alterations, translocations, and mutations associated with APOBEC cytidine deaminase activity. Despite maintained carcinogen exposure, tumors from smokers showed a relative decrease in smoking-related mutations over time, accompanied by an increase in APOBEC-associated mutations. In tumors from former smokers, genome-doubling occurred within a smoking-signature context before subclonal diversification, which suggested that a long period of tumor latency had preceded clinical detection. The regionally separated driver mutations, coupled with the relentless and heterogeneous nature of the genome instability processes, are likely to confound treatment success in NSCLC.