The Cancer Tree


By Jeffrey P. Townsend J. P. タウンゼンド
English 日本語 日本語
Biologists have long been studying genes to understand the history of branching on the tree of life, which unites all living creatures on earth—be they marmosets or microbes. One leaf on this sprawling ancestral tree, nestled among the apes, is Homo sapiens. Each individual in our species is an assemblage of cells, which cooperate to generate our body.  系統樹の分岐の歴史を理解するため,生物学者はかねて遺伝子を調べてきた。系統樹は地球上のすべての生き物を結びつけている「生命の樹」だ。祖先から枝分かれして生い茂るこの樹のなか,類人猿に囲まれた一枚の葉がホモ・サピエンスであり,私たちの身体は細胞の集まりから成り立っている。
Normally the cells obey a covenant, established by trial and error more than 600 million years ago, in the first forms of multicellular life. The covenant decrees that if cells are to live together, they have to follow basic rules: repair their DNA when it is damaged; listen to their neighbors about whether to divide or not; and stay in the tissue where they are supposed to be. Typically mutations that cause cells to violate these restrictions and start to grow and spread incessantly—the hallmarks of malignant cancer—are quashed by controlled death. The mutated cells detect their own problems and commit suicide or are killed by the immune system before they can do any harm.  その細胞は通常,ある誓約に従っている。いまから6億年以上前,最初の多細胞生物において試行錯誤の末に確立したルールで,細胞がともに生きるために従わねばならない基本的な規則を定めている。つまり,DNAが傷ついたら修復すること,細胞分裂するかどうかについて近隣の細胞の声を聞くこと,しかるべき組織にとどまり続けることだ。
On occasion, though, mutations accumulate against which the cellular surveillance system does not work, and tumors grow and spread. A malignant evolutionary tree sprouts within.  だが時には細胞の監視システムが機能せずに変異が蓄積し,腫瘍が拡大する場合がある。悪性の進化の枝が芽生えるのだ。
Researchers know of a few mutations that drive tumorigenesis, the formation of the initial tumor. What makes cancers particularly lethal, however, is metastasis, the escape of diseased cells from the primary tumor and into formerly healthy tissues, where they lodge to generate new tumors. In the belief that further mutations were required to propel metastasis and that these occurred relatively late in the history of the primary tumor, oncologists often sought to identify them and to target them with drugs.  腫瘍形成を促進する遺伝子変異がすでにいくつか知られている。だが,がんをとりわけ致命的なものにしているのは「転移」だ。がん細胞が原発腫瘍から抜け出し,それまで健康だった組織に侵出してそこに定着し,新たな腫瘍を生み出す。腫瘍学者はこれまで,転移が進むにはがん細胞にさらなる変異が加わることが必要で,それらは原発腫瘍の比較的遅い時期に生じると考えて,そうした変異を特定して治療薬の標的にしようとしてきた。
Around 2010, however, technological advances en­­abled scientists to inexpensively sequence the entire human genome (that is, to deduce the genome’s ordering of bases, or constituent units of DNA). Research groups at several institutions began to study the genetic sequences of tumors comprehensively. To their dismay, the investigators found that even within a single patient, the tumors often contained a baffling variety of mutations.  ところが2010年ころ,技術的進歩によってヒトゲノムの解析(DNAの構成単位である塩基の配列を調べること)が安価にできるようになり,いくつかの研究機関が腫瘍の遺伝子配列を包括的に調べ始めた。この結果,驚いたことに,同じ患者のなかでさえ,腫瘍が不可解なほど様々な変異を含んでいる場合が多いことがわかった。
Evolutionary biologists such as me see diversity as a source of valuable information, however. Along with colleagues at Yale University and other institutions, I decided to investigate how the mutations were related to one other. We sequenced the expressed portions of the genomes—those sections of DNA known to control the production of proteins and thereby to determine the properties of cells—of cancer patients. Further, we used that information to create evolutionary trees of the mutations associated with the disease. The branches of the trees illustrate how the genes within tumors change as the cancer grows from a few cells to a metastatic monster.  しかし私のような進化生物学者にとって,多様性は貴重な情報源だ。私はエール大学の同僚や他の機関の研究者とともに,こうしたがん細胞の変異が互いにどう関連しているかを調べることにした。私たちはがん患者のゲノムのうち,発現領域(タンパク質の産生を制御し,細胞の特性を決めることが知られているDNA部分)の配列を解読した。