Is carcinogenesis a form of speciation?
Is carcinogenesis a form of speciation?
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DOI：
10.4161/cc.10.13.16352
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发表时间：
2011-06-01
期刊：
影响因子：
4.3
通讯作者：
Nicholson, Joshua M.
中科院分区：
文献类型：
--
作者：
Duesberg, Peter;Mandrioli, Daniele;Nicholson, Joshua M.
由于癌症具有个体的克隆核型，是不朽的，只有在经过几个月到几十年的极长的潜伏期后，才能从经过致癌物处理的正常细胞进化而来--我们推断，癌症发生可能是物种形成的一种形式。这一理论认为，致癌物通过引起非整倍体，即染色体的丢失或获得来启动致癌。非整倍体破坏了核型的稳定，因为它破坏了数千个相互协作的基因的平衡，包括那些合成、分离和修复染色体的基因。在这种内在不稳定性的驱动下，非整倍体细胞自动进化出更随机的核型。大多数癌细胞死亡，但极少数获得了生殖自主性--这是癌细胞和物种的主要特征。在特定的变异范围内，针对非整倍体固有的不稳定性，自主选择稳定了新的癌症物种。物种形成理论解释了癌症的五个共同特征：(1)物种特定的自主性；(2)核型和表型个性；(3)在稳定的自主性范围内的核型变异带来的灵活性；(4)通过替换由这种灵活性产生的合格变异或亚种构成池中的有缺陷的核型来实现永生；以及(5)长肿瘤潜伏期，这是由于随机核型改变产生新的自主物种的可能性很低。此外，该理论解释了同一组织癌症之间的系统发育关系，因为癌症的发生受到组织特异性转录本的限制。这一理论也解决了其他癌症理论的悖论。例如，癌症的“非整倍体”现在被称为“悖论”或“癌症的致命缺陷”，因为非整倍体损害了正常的生长和发育。但是，如果癌症的“非整倍体”实际上是新物种的核型，这个悖论就解决了。
Since cancers have individual clonal karyotypes, are immortal and evolve from normal cells treated by carcinogens only after exceedingly long latencies of many months to decades-we deduce that carcinogenesis may be a form of speciation. This theory proposes that carcinogens initiate carcinogenesis by causing aneuploidy, i.e., losses or gains of chromosomes. Aneuploidy destabilizes the karyotype, because it unbalances thousands of collaborating genes including those that synthesize, segregate and repair chromosomes. Driven by this inherent instability aneuploid cells evolve ever-more random karyotypes automatically. Most of these perish, but a very small minority acquires reproductive autonomy-the primary characteristic of cancer cells and species. Selection for autonomy stabilizes new cancer species against the inherent instability of aneuploidy within specific margins of variation. The speciation theory explains five common characteristics of cancers: (1) species-specific autonomy; (2) karyotypic and phenotypic individuality; (3) flexibility by karyotypic variations within stable margins of autonomy; (4) immortality by replacing defective karyotypes from constitutive pools of competent variants or subspecies generated by this flexibility; and (5) long neoplastic latencies by the low probability that random karyotypic alterations generate new autonomous species. Moreover, the theory explains phylogenetic relations between cancers of the same tissue, because carcinogenesis is restricted by tissue-specific transcriptomes. The theory also solves paradoxes of other cancer theories. For example, "aneuploidy" of cancers is now said to be a "paradox" or "cancer's fatal flaw," because aneuploidy impairs normal growth and development. But if the "aneuploidies" of cancers are in effect the karyotypes of new species, this paradox is solved.