"哈士奇"的千古癌症 綿延1.1萬年

Scientists have sequenced the genome of the world's oldest continuously surviving cancer, a transmissible genital cancer that affects dogs. This cancer, which causes grotesque genital tumors in dogs around the world, first arose in a single dog that lived about 11,000 years ago. The cancer survived after the death of this dog by the transfer of its cancer cells to other dogs during mating. The genome of this 11,000-year-old cancer carries about two million mutations -- many more mutations than are found in most human cancers, the majority of which have between 1,000 and 5,000 mutations. The team used one type of mutation, known to accumulate steadily over time as a "molecular clock," to estimate that the cancer first arose 11,000 years ago.

一般來說，癌症在宿主體內產生後，會隨着宿主的死亡而灰飛煙滅。不過，據《科學》1月23日報道，有一脈“犬傳染性性病腫瘤”（CTVT）已經存在了1.1萬年，可能是有史以來最古老的癌症。該腫瘤的第一任宿主在品種上接近哈士奇，其基因至今仍保留在腫瘤細胞中。這一脈CTVT自1.1萬年前首次出現以後，非但沒有消亡，反而通過交配在犬類中廣泛傳播。這項研究已經在學術雜誌《科學》上面發表。科研人員已經完成了CTVT的基因排序工作，發現它已經有了大約200萬個變種。在人類中，癌症的變種一般在1000至5000個之間。研究團隊分析了其中一個變種，認定CTVT最早出現在1.1萬年之前。

"The genome of this remarkable long-lived cancer has demonstrated that, given the right conditions, cancers can continue to survive for more than 10,000 years despite the accumulation of millions of mutations," says Dr Elizabeth Murchison, first author from the Wellcome Trust Sanger Institute and the University of Cambridge. The genome of the transmissible dog cancer still harbors the genetic variants of the individual dog that first gave rise to the cancer 11,000 years ago. Analysis of these genetic variants revealed that this dog may have resembled an Alaskan Malamute or Husky. It probably had a short, straight coat that was colored either grey/brown or black. Its genetic sequence could not determine if this dog was a male or a female, but did indicate that it was a relatively inbred individual.

論文第一作者、來自劍橋大學的伊麗莎白?默奇森博士說：“這個癌症如此長壽，實在難得。它的基因說明，在適當的環境下，癌症能夠存活1萬年以上，並衍生出數百萬個變種。”這個癌症基因至今仍保有1.1萬年前其首任宿主的基因。分析表明，這位“始作俑者”在品種上和哈士奇非常相似，毛髮短而直，可能以灰、褐、黑等顏色爲主。默奇森說：“我們不知道爲什麼這一條狗會患上傳染性癌症。”

"We do not know why this particular individual gave rise to a transmissible cancer," says Dr Murchison, "But it is fascinating to look back in time and reconstruct the identity of this ancient dog whose genome is still alive today in the cells of the cancer that it spawned." Transmissible dog cancer is a common disease found in dogs around the world today. The genome sequence has helped scientists to further understand how this disease has spread. "The patterns of genetic variants in tumors from different continents suggested that the cancer existed in one isolated population of dogs for most of its history," says Dr Murchison. "It spread around the world within the last 500 years, possibly carried by dogs accompanying seafarers on their global explorations during the dawn of the age of exploration."

談及CTVT的傳播史時，默奇森說：“不同大陸上腫瘤變種的範式表明，腫瘤長期侷限在一個孤立的犬類種羣裏，在過去500年內纔在全世界傳播開來。這些犬類也許是在探險時代的早期跟隨主人們周遊世界的。” 自然環境下的傳染性癌症非常罕見。癌症能夠在宿主的不同器官中擴散，但很難傳染給其他個體。作者之一麥克?斯特拉頓說：“這個傳染性犬類癌症的基因會幫助我們研究癌症傳染的過程。雖然傳染性癌症非常罕見，但我們必須做好準備，以防類似疾病在人類或者其他動物中出現。另外，通過研究這個古老的癌症，我們能夠更加廣泛地瞭解影響癌症進化的因素。

Transmissible cancers are extremely rare in nature. Cancers, in humans and animals, arise when a single cell in the body acquires mutations that cause it to produce more copies of itself. Cancer cells often spread to different parts of the body in a process known as metastasis. However, it is very rare for cancer cells to leave the bodies of their original hosts and to spread to other individuals. Apart from the dog transmissible cancer, the only other known naturally occurring transmissible cancer is an aggressive transmissible facial cancer in Tasmanian devils that is spread by biting. "The genome of the transmissible dog cancer will help us to understand the processes that allow cancers to become transmissible," says Professor Sir Mike Stratton, senior author and Director of the Sanger Institute. "Although transmissible cancers are very rare, we should be prepared in case such a disease emerged in humans or other animals. Furthermore, studying the evolution of this ancient cancer can help us to understand factors driving cancer evolution more generally."

美國國家衛生研究院的癌症遺傳學家伊萊恩?奧斯特蘭德說：“這絕對令人興奮。成千上萬年來，犬類一直傳播、照顧這一脈的癌症細胞，現在我們有機會研究它了。