Man's Best Friend for Driver-Passenger Distinction

人类最好的区分驾驶员和乘客的朋友

基本信息

批准号：
8762040
负责人：
SHAYING ZHAO
金额：
$ 30.92万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8762040
关键词：
Accounting Address Anchorage-Independent Growth Automobile Driving Awareness Biological Process Cancer Etiology Candidate Disease Gene Canis familiaris Carcinoma Cell Line Cell Proliferation Classification Colorectal Cancer Colorectal Neoplasms Companions DNA Sequence Rearrangement Data Databases Discrimination Epithelial Freezing Genes Genome Genomics Human Large Intestine Carcinoma Lead Location Malignant Neoplasms Measures Microdissection Microsatellite Instability Molecular Molecular Carcinogenesis Mutate Nude Mice Orthologous Gene PPP3CA gene Pathogenesis Pathway Analysis Pathway interactions Patients Pilot Projects Proteins Publishing Quality Control Reporting Resources Role Sampling Sequence Analysis Solid Source The Cancer Genome Atlas Therapeutic Intervention Tumorigenicity Xenograft procedure anticancer research anticancer treatment cancer genomics cell motility comparative comparative genomics fusion gene gene function genome sequencing next generation sequencing novel oncology public health relevance small hairpin RNA success transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): We propose herein to use a novel human-dog spontaneous cancer comparative genomics and oncology strategy to discriminate cancer drivers from passengers for the >7000 amplified/deleted genes reported by TCGA for human colorectal cancer (CRC). Our published proof-of-principle studies have shown that spontaneous canine CRCs indeed share similar molecular carcinogenesis pathways with their human counterparts. In addition, we have also successfully validated this novel human-dog comparison strategy in a pilot study. For the proposed project, we will first identify altered genes in ~100 canine spontaneous carcinomas that are microsatellite instability (MSI)-negative, with state-of-the-art next generation sequencing analysis approaches. Then, we will compare our findings to those reported by TCGA for driver-passenger discrimination. The proposed study will lead to a significant advancement beyond the TCGA findings. Its success will present an effective strategy to address a central aim of cancer research, opening up novel avenues for future research and for the use of vast amounts of cancer genomic data rapidly accumulated. The findings will contribute to the understanding of CRC etiology and yield effective targets for therapeutic intervention of this prevalent cancer. Finally, the project will significantly raise awareness of spontaneous cancers in companion dogs, an immensely valuable yet greatly understudied and underutilized resource in human cancer research.

描述（由申请人提供）：我们在本文中建议使用一种新型的人类自发性癌症比较基因组学和肿瘤策略来区分乘客的癌症驱动因素，以> 7000个由TCGA报道的人类结直肠癌（CRC）报道的> 7000个扩增/删除基因（CRC）。我们发表的原理证明研究表明，自发的犬CRC确实与人类对应物具有相似的分子癌变途径。此外，在一项试点研究中，我们还成功验证了这种新型的人类狗比较策略。对于拟议的项目，我们将首先鉴定出约100个犬自发性癌中的改变的基因，这些癌是微卫星不稳定性（MSI）阴性，并采用最新的下一代测序分析方法。然后，我们将将我们的发现与TCGA报告的驾驶员歧视歧视的发现进行比较。拟议的研究将导致超出TCGA发现以外的重大进步。它的成功将提出一种有效的策略，以解决癌症研究的核心目标，为未来研究和使用大量癌症基因组数据迅速积累的新途径。这些发现将有助于理解CRC病因，并产生对这种普遍癌症治疗干预的有效靶标。最后，该项目将大大提高对伴侣狗的自发癌的认识，这是一种非常有价值但已被大量研究和未充分利用的人类癌症研究资源。