“哈士奇”的千古癌症 绵延1.1万年

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.

"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.

"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."

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."

一般来说，癌症在宿主体内产生后，会随着宿主的死亡而灰飞烟灭。不过，据《科学》1月23日报道，有一脉“犬传染性性病肿瘤”（CTVT）已经存在了1.1万年，可能是有史以来最古老的癌症。该肿瘤的第一任宿主在品种上接近哈士奇，其基因至今仍保留在肿瘤细胞中。

这一脉CTVT自1.1万年前首次出现以后，非但没有消亡，反而通过交配在犬类中广泛传播。这项研究已经在学术杂志《科学》上面发表。科研人员已经完成了CTVT的基因排序工作，发现它已经有了大约200万个变种。在人类中，癌症的变种一般在1000至5000个之间。研究团队分析了其中一个变种，认定CTVT最早出现在1.1万年之前。

论文第一作者、来自剑桥大学的伊丽莎白•默奇森博士说：“这个癌症如此长寿，实在难得。它的基因说明，在适当的环境下，癌症能够存活1万年以上，并衍生出数百万个变种。”

这个癌症基因至今仍保有1.1万年前其首任宿主的基因。分析表明，这位“始作俑者”在品种上和哈士奇非常相似，毛发短而直，可能以灰、褐、黑等颜色为主。默奇森说：“我们不知道为什么这一条狗会患上传染性癌症。”

谈及CTVT的传播史时，默奇森说：“不同大陆上肿瘤变种的范式表明，肿瘤长期局限在一个孤立的犬类种群里，在过去500年内才在全世界传播开来。这些犬类也许是在探险时代的早期跟随主人们周游世界的。”

自然环境下的传染性癌症非常罕见。癌症能够在宿主的不同器官中扩散，但很难传染给其他个体。作者之一麦克•斯特拉顿说：“这个传染性犬类癌症的基因会帮助我们研究癌症传染的过程。虽然传染性癌症非常罕见，但我们必须做好准备，以防类似疾病在人类或者其他动物中出现。另外，通过研究这个古老的癌症，我们能够更加广泛地了解影响癌症进化的因素。

美国国家卫生研究院的癌症遗传学家伊莱恩•奥斯特兰德说：“这绝对令人兴奋。成千上万年来，犬类一直传播、照顾这一脉的癌症细胞，现在我们有机会研究它了。”