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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）：我们在此提出使用一种新的人犬自发癌比较基因组学和肿瘤学策略来区分TCGA报道的人类结直肠癌(CRC) >7000扩增/缺失基因的癌症驱动者和乘客。我们发表的原理证明研究表明，犬类自发的crc确实与人类具有相似的分子致癌途径。此外，我们还在试点研究中成功验证了这种新颖的人狗比较策略。在拟议的项目中，我们将首先使用最先进的下一代测序分析方法，在约100例微卫星不稳定性（MSI）阴性的犬自发性癌中识别改变的基因。然后，我们将我们的研究结果与TCGA报告的司机-乘客歧视进行比较。拟议的研究将导致TCGA研究结果之外的重大进展。它的成功将为解决癌症研究的中心目标提供一种有效的策略，为未来的研究开辟新的途径，并为利用迅速积累的大量癌症基因组数据开辟新的途径。这些发现将有助于了解结直肠癌的病因，并为这种常见癌症的治疗干预提供有效的靶点。最后，该项目将显著提高人们对伴侣犬自发性癌症的认识，这是人类癌症研究中非常宝贵但尚未得到充分研究和利用的资源。