Browning Helen M, Acevedo-Whitehouse Karina, Gulland Frances M D, Hall Ailsa J, Finlayson Jeanie, Dagleish Mark P, Billington Karen J, Colegrove Kathleen, Hammond John A
Sea Mammal Research Unit, Scottish Oceans Institute, University of St Andrews, Fife, UK.
Unit for Basic and Applied Microbiology, Autonomous University of Querétaro, Querétaro, Mexico.
Proc Biol Sci. 2014 Dec 7;281(1796):20140240. doi: 10.1098/rspb.2014.0240.
Although neoplasia is a major cause of mortality in humans and domestic animals, it has rarely been described in wildlife species. One of the few examples is a highly prevalent urogenital carcinoma in California sea lions (CSLs). Although the aetiology of this carcinoma is clearly multifactorial, inbreeding depression, as estimated using levels of microsatellite multilocus heterozygosity, is identified as predictive for this neoplasia. On further analysis, this relationship appears to be largely driven by one marker, suggesting that a single locus might be associated with the occurrence of this disease in CSLs. In a case-control study, carcinoma was significantly associated with homozygosity at the Pv11 microsatellite locus. Pv11 was mapped to intron 9 of the heparanase 2 gene (HPSE2) locus, a very large gene encoding heparanase 2, which in humans is associated with multiple carcinomas. Correspondingly, immunohistochemical labelling in tissues was present in carcinoma cases within a single homozygous Pv11 genotype. To our knowledge, this is the first report of an individual locus being associated with cancer in any wildlife species. This adds emphasis to the study of HPSE2 in other species, including humans and will guide future studies on this sentinel species that shares much of its diet and environment with humans.
尽管肿瘤形成是人类和家畜死亡的主要原因，但在野生动物物种中却很少被描述。少数例子之一是加利福尼亚海狮（CSL）中高度流行的泌尿生殖系统癌。尽管这种癌的病因显然是多因素的，但使用微卫星多位点杂合性水平估计的近亲繁殖衰退被确定为这种肿瘤形成的预测因素。进一步分析表明，这种关系似乎主要由一个标记驱动，这表明单个基因座可能与CSL中这种疾病的发生有关。在一项病例对照研究中，癌与Pv11微卫星基因座的纯合性显著相关。Pv11被定位到乙酰肝素酶2基因（HPSE2）基因座的第9内含子，HPSE2是一个非常大的编码乙酰肝素酶2的基因，在人类中与多种癌症相关。相应地，在单个纯合Pv11基因型的癌病例中，组织中的免疫组化标记呈阳性。据我们所知，这是在任何野生动物物种中首次报道单个基因座与癌症相关。这进一步强调了在包括人类在内的其他物种中对HPSE2的研究，并将指导对这种与人类共享许多饮食和环境的哨兵物种的未来研究。
