Genomic Predictors of Oral Premalignancy Progression

描述（由申请人提供）：本K22申请旨在支持Xiaofeng Charles Zhou博士的学术培训和职业发展，使其成为头颈部癌症研究的独立研究者。该申请详细说明了该提案在候选人，导师，职业发展计划，环境和研究计划方面的优势和独特性。 拟议的研究是为了验证这一假设，即存在区分进展性口腔癌前病变和非进展性口腔癌前病变的基因组决定因素。所有级别的口腔癌前病变恶变的总体风险约为18%。根据传统的临床和组织学特征，不可能预测任何一种病变的进展。基于基因组学的新分类对于区分进展性和非进展性口腔癌前病变至关重要。该研究旨在确定进展性和非进展性口腔癌前病变的全基因组差异等位基因失衡（洛）特征。具体目标1是建立和优化一系列创新的新兴基因组工具，连续用于口腔癌前病变的体内应用。这将在学者发展阶段（2年）完成。具体目标2将在学院过渡阶段进行，目的是确定进展和非进展口腔癌前病变的全基因组洛谱，并产生用于预测口腔癌前病变进展的分子分类。具体目标3是在所鉴定的洛缺失区域中鉴定口腔癌前进展的候选基因。功能和生物学测试是适当的，以评估候选基因对肿瘤进展过程的功能贡献。 一个职业发展计划已经到位，为转化头颈癌研究的候选人做好准备。定义和评估的里程碑是到位，以评估候选人的科学进展，特别是在过渡到学院过渡阶段。除了研究培训外，候选人还将接受生物伦理学和负责任的研究，口腔病理学，生物统计学和赠款写作方面的教学培训。该奖项的结果将是一个准备充分和有竞争力的年轻科学家致力于翻译头颈癌研究的职业生涯。

DESCRIPTION (provided by applicant): This K22 application is to support the scholarly training and career development of Dr. Xiaofeng Charles Zhou to become an independent investigator in head and neck cancer research. This application details the strengths and uniqueness of this proposal pertaining to the candidate, the mentor, the career development plan, the environment and the research plan. The proposed research is to test the hypothesis that there are genomic determinants that distinguish progressing from non-progressing oral precancers. The overall risk of malignant transformation of all grades of oral precancers is approximately 18%. It is impossible to predict progressiveness of any one lesion based on conventional clinical and histological features. Genomic-based new classifications are essential to distinguish the progressing from non-progressing oral precancers. The proposed research aims to determine genome-wide differential allelic imbalance (LOH) profiles for progressing and non-progressing oral precancers. Specific Aim 1 is to establish and optimize a series of innovative emerging genomic tools, to be used consecutively for the application on oral precancers in vivo. This will be accomplished during the Scholar Development Phase (2 years). Specific Aim 2, to be performed in the Faculty Transition Phase, is to determine the genome wide LOH profiles in progressing and non-progressing oral precancers and generate molecular classification for the prediction of oral precancer progression. Specific Aim 3 is to identify candidate genes for oral precancer progression in the identified LOH regions. Functional and biological tests are in place to evaluate the functional contribution of candidate genes to the tumor progression process. A career development plan is in place to prepare the candidate for translational head and neck cancer research. Defined and evaluative milestones are in place to assess the scientific progress of the candidate, particularly during transition to the Faculty Transition Phase. In addition to the research training, the candidate will receive didactic training in bioethics and responsible conduct of research, oral pathology, biostatistics, and grant writing. The outcome of this award will be a well prepared and competitive young scientist committed to a career in translational head and neck cancer research.