癌症的起源-看我72变
关键词： 癌症，起源There are a lot more cancer genes around than were previously known
致癌基因事实上远比我们过去所知的多上许多。
THE purpose of cells is to increase and multiply. That is what they do best. That, indeed, is a pretty good definition of being alive. Stopping a cell dividing into two, then four, then eight is hard. But in multicellular organisms it is essential, otherwise anarchy reigns. So special genes devoted to the task have evolved. It is when these genes mutate and go wrong that cancer develops.
细胞是为了增殖而存在，而它们也精于此道，甚至增殖是生物活着的一种证明。让一个细胞停止二分裂（一生二，二生四，四变八）是很困难的。但在多细胞生物的体内，为了避免混乱，细胞不能随意增殖。而达到这种目的则需人体内一些特殊的基因参与其中。因此，当这些基因突变或是出现问题时，随之而来的就是癌症。
Knowing all the genes whose mutation is involved in cancer would help researchers understand natural anti-cancer mechanisms and thus design better diagnoses and treatments. Until now, though, such genes have been discovered piecemeal, so no one knows how many there are. To overcome that ignorance, Victor Velculescu and his colleagues at the Johns Hopkins Kimmel Cancer Centre in Baltimore are starting a programme to look for all possible mutant genes in tumours, by comparing the DNA of healthy and cancerous cells. Their first results have been published in this week's Science.
掌握哪些基因的突变导致了癌症将会让科学家们对人体先天抗癌机制有更进一步的理解，从而推动更加有效的诊断及治疗方法的研发。直到现在，只是零星地发现这类基因，因此这些基因的数量仍旧是未知数。为了改变这种现状Victor Velculescu和他的研究成员在位于巴尔的摩的Johns Hopkins Kimmel癌症中心，开展了一项通过对比正常细胞与癌细胞DNA差异来寻找肿瘤发生时可能变异基因的研究。他们的第一批成果已登载在这周出版的《Science》杂志上。
Dr Velculescu's group has begun by studying breast and colorectal cancers, which together account for 20% of cancer diagnoses. They took 11 different samples of each of the two sorts of cancer and searched for mutated genes in them. They focused their efforts on just over 13,000 genes that have been well enough studied by the Human Genome Project for their DNA sequences to be known accurately. Obtaining the details of these genes from the genome project's databases made it possible for the researchers to locate and make copies of each relevant gene from each cancer sample. They then ran those copies through DNA-sequencing machines to see how the samples' genes differed from the reference genes.
Velculescu博士的团队的研究从占全部肿瘤发病20%的乳腺癌及直肠癌开始。他们在这两种肿瘤的11不同个体样本中寻找变异的基因。为了使他们充份了解所要研究的基因片段，他们工作的重心放在已被人类基因组计划充分研究的13，000段基因片段。从人类基因组计划数据库中获取基因的信息可以帮助科学家对肿瘤样本中的相关基因进行定位和拷贝。然后通过对这些基因的拷贝进行序列测定，最终得出肿瘤样本中的基因与正常基因的不同之处。
Go forth and multiply勇往直前地分裂
To start with, they found hundreds of thousands of differences, but many of these could be winnowed away. For example, a lot of changes in genes do not actually affect the composition of the protein for which that gene is a recipe. Such “silent” mutations can be ignored since, as they do not change the protein, they do not have much biological effect. There is also a certain amount of natural variation. Not all deviations from the genome project's reference sequences are harmful mutations. Many are harmless and widespread. A lot of these harmless alternatives are listed in another database. They, too, were screened out.
开始的时候，他们发现几十万个不同之处，但其中很多被筛选了下去。例如，很多并非是编码的基因，而其结构改变对蛋白的合成不构成任何影响。由于这些“中性”突变对蛋白的合成不构成影响，即没有生物学活性，因此这些中性突变的基因在研究中被忽略不计。除此之外自然的变异无处不在，所以并不是所有通过基因测序得到变异都是有害的变异。无害的突变的存在相当广泛。无害的基因变异被存储在另外一个数据库中，自然被列在研究对象之外。
Once that had been done, the remaining potentially harmful mutations in each subject's cancer were checked against his healthy tissue, to see which mutations existed throughout his body and were thus not associated with the disease. Finally, the team found 24 more people with breast cancer and 24 with colorectal cancer, and looked at their tumours for the mutant genes that had got through the screening. If at least one of the newly selected tumours also had a mutated version of one of the genes in question, that gene was reckoned a good candidate as a tumour-causing gene. Or, more accurately, as a contributory cause. For one point about anticancer genes is that several have to go wrong in the same cell before a tumour can grow.
接下来的工作是，将在各种癌症中影响蛋白合成的基因突变与正常组织的基因相比，排除全身都存在，即与该疾病无关的突变。最后，研究小组又分别检查24名患乳腺癌和直肠癌的患者，在这些患者的肿瘤中寻找通过层层筛选所得知的突变基因。只要有一个新选择的肿瘤样本中的“问题”（通过实验得知）基因也发生了突变，该基因是致癌基因的机率越高。从另一方面说，在肿瘤发生之前该细胞的抑癌基因出现了失活。
Dr Velculescu and his colleagues found about 190 genes that passed all the tests. Encouragingly, these included the previously known culprits among the two cancers in question. They also included dozens of new ones.
Velculescu博士和他的研究人员在全部测试结束后发现了190个该类基因。令人兴奋的是，除了两个癌症一部分过去已知的“罪魁祸首”，他们还发现了几十个新的基因。
The mutated genes in breast cancers and colorectal cancers were almost completely distinct, suggesting the two cancers develop along different pathways. But within the two broad groups of cancer, any particular tumour had its own set of mutations. Breast cancers had between four and 23, with an average of 12. Colorectal cancers had between three and 18, with an average of nine.
导致乳腺癌与直肠癌的变异基因截然不同也就说明这两种癌症的发病机制有着很大的差异。尽管每个癌症的个案都有一套独自的突变组合，但这两大类癌症发生突变的基因是确定的。乳腺癌有4-23个突变的基因，平均12个；直肠癌则是3-18个，平均9个。
That emphasises something that oncologists have long believed, namely that almost every individual case of cancer—not merely every type of cancer—is likely to be different. This helps to explain differences in the outcome of identical treatments for apparently identical cancers: at the genetic level those cancers are not identical at all. How long that observation will take to translate into personalised treatment is anybody's guess.
那就强调了为肿瘤学家们长期以来一直所相信的，不仅是不同种类，甚至是不同的病例，癌症看起来都是不同的。因此在临床上，不同的患者应用不同的疗法：但在基因水平各种癌症完全失去了那种个体特异性。而何时这项研究可以应用于个人医疗还是未知。
翻译 by mickey2050
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