米格鲁猎犬帮助寻找与狗相关的基因, Human Bladder Cancer

Beagles aren’t just one of America’s most popular dog breeds. According to new research from North Carolina State University, they’re also key to new findings about the chromosomal changes associated with urothelial carcinoma, or bladder cancer. These findings could lead to better diagnostic tests for both canine and human patients.

尿路上皮癌是两种犬和人类膀胱癌最常见的形式，而某些狗（Beagles，Shelties和几种梗犬）比其他狗更容易发生这种疾病。据估计，每年的犬类种群中估计有40,000例新的膀胱癌病例发生（人类每年约有74,000例新病例）。由于症状通常模仿常规膀胱感染和良性病变的症状，因此这种疾病很难尽早发现。

Adding to the difficulty of diagnosing the disease is the fact that there is some evidence that performing biopsies on suspicious masses in dogs can lead to spread of the disease and make the cancer harder to treat. “Bladder cancer is relatively treatable and median survival with standard of care therapy is generally around seven months, though about 20 percent of dogs can live for over a year,” says Matthew Breen, professor of genomics at NC State and senior author of a paper describing the research. “A confirmed diagnosis generally needs a biopsy specimen, but obtaining these may cause the cancer to disperse across the bladder. What we need is an accurate means of diagnosis with a specimen that is both noninvasive and easy to collect, such as a sample of free-catch urine.”

Breen and a team of researchers from NC State decided to look at the genomes of the canine tumors to identify a signature that would identify these cancers. Susan Shapiro, a DVM/Ph.D student in comparative biomedical sciences and the paper’s lead author, evaluated a series of canine specimens, isolated DNA samples from dogs with bladder cancer, and looked for genetic similarities.

“We found that in all cases of urothelial carcinoma we evaluated there was an aberrant number of copies of three particular canine chromosomes: 13, 19, and 36,” Shapiro says. “Dogs with bladder cancer would either gain extra copies of chromosomes 13 or 36, or lose one or both copies of chromosome 19.

“These were really exciting findings for us, since all patients showed at least one of these chromosome changes and most commonly a combination of the three,” Shapiro adds. “I’m really optimistic that these findings can help us create a reliable diagnostic test to help clinicians catch tumors before they become aggressive and serve as a screening test for predisposed breeds.”

布雷恩（Breen）决定将信息进一步迈出一步，并确定犬数据的价值，以推动对人膀胱癌的了解。该小组与犹他大学的一群人合作，由儿科肿瘤学家约书亚·希夫曼（Joshua Schiffman）合作，将犬类基因组映射到了人类。布雷恩说：“我们能够从狗中获取遗传信息并将其重新排列，以便它将其完全映射到人类的基因组。”“然后，我们查看人类基因组上的犬'故障点'的位置，它有助于我们缩小寻找可能在癌症中发挥作用的基因的搜索。”在Schiffman实验室的意见下，Breen和他的团队发现了一个位于人类染色体上的基因，称为PABPC1that looks very promising for both dogs and humans.

“The fact that we know with almost 100 percent certainty what to look for chromosomally in canine bladder cancer means that we are now are well on the way to developing a highly effective and noninvasive assay for early detection of canine bladder tumors” Breen says. “And the identification ofPABPC1as associated with bladder cancer in both dogs and humans may help us with early detection and better treatment options for those patients as well.”

The results appear inChromosome Research (doi:10.1007/s10577-015-9471-y). Funding was provided by the Skippy Frank Fund for Life Sciences and Translational Research/ Rockefeller Philanthropy Advisors, the National Institutes of Health and the NCSU-CVM Cancer Genomics Fund.