对于研究癌症的科学家来说，最主要的挑战就是弄清楚癌症扩散的元凶，从而辨别出成千上万的癌细胞的基本突变。
采用了一种叫做“全基因组剖析”的新技术,麻省理工大学的科学家们已经确认了一种基因，它似乎能够控制小的肺癌细胞，这种侵略性的形式似乎占了所有肺癌病例的15%。
Alison Dooley，麻省理工学院David H. Koch综合癌症研究机构的主任说，“研究人员发现这种基因在老鼠和人类的肺部肿瘤中同时存在，并且非常活跃，有可能成为新药物研究的新方向。”Dooley是这项研究的主导者，其研究论文发表在7月15日的《基因和发展》杂志上。
经过5年的临床诊断，这种小的肺癌细胞杀死了大约95%的患者，但是科学家们仍然没有弄清楚到底是哪些基因在控制它。Dooley和她的同事们研究了一只老鼠的疾病进展情况，从而删除了两种关键的抑癌基因：p53和Rb。Dooley说,“老鼠的模式也类似于人类的疾病，它的癌肿瘤也非常活跃，扩散到人类癌症也经常扩散的地方，例如肝脏和肾上腺。”
这种模式让科学家们从头至尾地跟踪疾病的进展，但是科学家们却无法这样跟踪人类，因为这种快速扩散的疾病被发现的时候经常是晚期了。使用“全基因组剖析”,研究人员就能够识别部分被复制或删除的癌症老鼠的染色体。
他们发现在DNA上有一些小的多余的复制品，包括4号染色体的一部分，它含有叫做核转录因子I / B(NFIB)的单个基因。这是NFIB第一次被检测出与小细胞肺癌相关,尽管它在一项老鼠实验中被证实与前列腺癌有关。该基因的确切作用还不为人所知，但是它却导致肺癌细胞的扩散。其他实验室中研究人类癌细胞的研究人员也发现了相似的结论，发现NFIB能够引起人类肺癌细胞的扩散。约翰霍普金斯大学医学院的肿瘤学教授Barry Nelkin也说到，“NFIB确实在人类肺癌细胞中发挥中重要的作用。”尽管他没有参与到这项研究中。目前，研究人员正在寻找被NFIB控制的基因，如果能找出那些基因，也许能为小细胞肺癌治疗提供新的方向。
生物探索推荐英文原文：
New Lung-Cancer Gene Found: Cancer Biologists Identify a Driving Force Behind the Spread of an Aggressive Type of Lung Cancer
A major challenge for cancer biologists is figuring out which among the hundreds of genetic mutations found in a cancer cell are most important for driving the cancer's spread.
Using a new technique called whole-genome profiling, MIT scientists have now pinpointed a gene that appears to drive progression of small cell lung cancer, an aggressive form of lung cancer accounting for about 15 percent of lung cancer cases.
The gene, which the researchers found overexpressed in both mouse and human lung tumors, could lead to new drug targets, says Alison Dooley, a recent PhD recipient in the lab of Tyler Jacks, director of MIT's David H. Koch Institute for Integrative Cancer Research. Dooley is the lead author of a paper describing the finding in the July 15 issue of Genes and Development.
Small cell lung cancer kills about 95 percent of patients within five years of diagnosis; scientists do not yet have a good understanding of which genes control it. Dooley and her colleagues studied the disease's progression using a strain of mice, developed in the laboratory of Anton Berns at the Netherlands Cancer Institute, that deletes two key tumor-suppressor genes, p53 and Rb.
"The mouse model recapitulates what is seen in human disease. It develops very aggressive lung tumors, which metastasize to sites where metastases are often seen in humans," such as the liver and adrenal glands, Dooley says.
This kind of model allows scientists to follow the disease progression from beginning to end, which can't normally be done with humans because the fast-spreading disease is often diagnosed very late. Using whole-genome profiling, the researchers were able to identify sections of chromosomes that had been duplicated or deleted in mice with cancer.
They found extra copies of a few short stretches of DNA, including a segment of chromosome 4 that turned out to include a single gene called Nuclear Factor I/B (NFIB). This is the first time NFIB has been implicated in small cell lung cancer, though it has been seen in a mouse study of prostate cancer. The gene's exact function is not known, but it is involved in the development of lung cells.
Researchers in Jacks' lab collaborated with scientists in Matthew Meyerson's lab at the Dana-Farber Cancer Institute and the Broad Institute to analyze human cancer cells, and found that NFIB is also amplified in human small cell lung tumors.
That makes a convincing case that the gene truly is playing an important role in human small cell lung cancer, says Barry Nelkin, a professor of oncology at Johns Hopkins University School of Medicine, who was not involved in this research.
"The question, always, with mouse models is whether they can tell you anything about a human disease," Nelkin says. "Some tell you something, but in others, there may be only a similarity in behavior, and the genetic changes are nothing like what is seen in humans."
The NFIB gene codes for a transcription factor, meaning it controls the expression of other genes, so researchers in Jacks' lab are now looking for the genes controlled by NFIB. "If we find what genes NFIB is regulating, that could provide new targets for small cell lung cancer therapy," Dooley says.A major challenge for cancer biologists is figuring out which among the hundreds of genetic mutations found in a cancer cell are most important for driving the cancer's spread.
Using a new technique called whole-genome profiling, MIT scientists have now pinpointed a gene that appears to drive progression of small cell lung cancer, an aggressive form of lung cancer accounting for about 15 percent of lung cancer cases.
The gene, which the researchers found overexpressed in both mouse and human lung tumors, could lead to new drug targets, says Alison Dooley, a recent PhD recipient in the lab of Tyler Jacks, director of MIT's David H. Koch Institute for Integrative Cancer Research. Dooley is the lead author of a paper describing the finding in the July 15 issue of Genes and Development.
Small cell lung cancer kills about 95 percent of patients within five years of diagnosis; scientists do not yet have a good understanding of which genes control it. Dooley and her colleagues studied the disease's progression using a strain of mice, developed in the laboratory of Anton Berns at the Netherlands Cancer Institute, that deletes two key tumor-suppressor genes, p53 and Rb.
"The mouse model recapitulates what is seen in human disease. It develops very aggressive lung tumors, which metastasize to sites where metastases are often seen in humans," such as the liver and adrenal glands, Dooley says.
This kind of model allows scientists to follow the disease progression from beginning to end, which can't normally be done with humans because the fast-spreading disease is often diagnosed very late. Using whole-genome profiling, the researchers were able to identify sections of chromosomes that had been duplicated or deleted in mice with cancer.
They found extra copies of a few short stretches of DNA, including a segment of chromosome 4 that turned out to include a single gene called Nuclear Factor I/B (NFIB). This is the first time NFIB has been implicated in small cell lung cancer, though it has been seen in a mouse study of prostate cancer. The gene's exact function is not known, but it is involved in the development of lung cells.
Researchers in Jacks' lab collaborated with scientists in Matthew Meyerson's lab at the Dana-Farber Cancer Institute and the Broad Institute to analyze human cancer cells, and found that NFIB is also amplified in human small cell lung tumors.
That makes a convincing case that the gene truly is playing an important role in human small cell lung cancer, says Barry Nelkin, a professor of oncology at Johns Hopkins University School of Medicine, who was not involved in this research.
"The question, always, with mouse models is whether they can tell you anything about a human disease," Nelkin says. "Some tell you something, but in others, there may be only a similarity in behavior, and the genetic changes are nothing like what is seen in humans."
The NFIB gene codes for a transcription factor, meaning it controls the expression of other genes, so researchers in Jacks' lab are now looking for the genes controlled by NFIB. "If we find what genes NFIB is regulating, that could provide new targets for small cell lung cancer therapy," Dooley says.
