Molecular Pathology of Cancer

癌症的分子病理学

• 批准号: 8938423
• 负责人: Michael Emmert-Buck
• 金额: $ 51万
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8938423
• 关键词: 13q12; Affect; Allelotyping; Androgens; Biotechnology; CCR; Candidate Disease Gene; China; Chromosome Band; Clinical; Data; Development; Diabetes Mellitus; Digestive System Disorders; Disease; Epigenetic Process; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Evaluation; Family history of; Gene Expression; Genes; Genomics; Goals; Human; Individual; Inherited; Institutes; Kidney Diseases; Malignant Neoplasms; Malignant neoplasm of prostate; Measurement; Menin; Methylation; Molecular; Molecular Profiling; Multiple Endocrine Neoplasia Type 1; National Human Genome Research Institute; Nature; Neuroendocrine Tumors; Pathogenesis; Patients; Population; Proteins; Province; Specimen; Syndrome; Therapeutic Intervention; Transcript; Tumor Suppressor Genes; United States National Institutes of Health; Urologic Oncology; base; cancer prevention; high risk; human tissue; interest; molecular pathology; new technology; novel diagnostics; prognostic; prostate carcinogenesis; tumor; tumor microenvironment; working group

As part of an integrated effort between the Pathogenetics Unit and the Urologic Oncology Branch, CCR, we identified a large number of deregulated transcripts and proteins in human prostate cancer, including a gene set that segregates high- and moderate grade cancer, and a gene set that segregates androgen-dependent and androgen-independent disease. Efforts are continuing to better understand the molecular nature of prostate tumorigenesis, and to identify gene expression profiles associated with clinically aggressive cancer. Additionally, we discovered a new type of epigenetic methylation field in prostate cancer that may assist in understanding the pathogenesis of the tumor microenvironment. In a search for genes involved in the development of esophageal tumors, we are collaborating with the Cancer Prevention Studies Branch, CCR, to examine the molecular basis of esophageal squamous cell carcinoma (ESCC) in a high-risk population in Shanxi province in China. Allelotype comparison of patients with and without a family history of ESCC identified a region on chromosome band 13q12 that may harbor a familial tumor suppressor gene. Efforts are underway to analyze several candidate genes in the genomic region of interest. Multiple Endocrine Neoplasia Type I (MEN1) is an inherited syndrome characterized by development of neuroendocrine tumors in affected individuals. The responsible gene was discovered in 1997 by the NIH MEN1 working group, including the Pathogenetics Unit and groups from the National Human Genome Research Institute, the National Center for Biotechnology Information, and the National Institute of Diabetes and Digestive and Kidney Diseases. Current efforts of the Pathogenetics Unit include immunohistochemical evaluation of menin in human tissues.

作为病理遗传学部门和泌尿肿瘤科 (CCR) 之间综合努力的一部分，我们在人类前列腺癌中鉴定出了大量失调的转录本和蛋白质，包括分离高级别和中级别癌症的基因集，以及分离高级别和中级别癌症的基因集区分雄激素依赖性和雄激素非依赖性疾病。人们正在继续努力更好地了解前列腺肿瘤发生的分子性质，并确定与临床侵袭性癌症相关的基因表达谱。此外，我们在前列腺癌中发现了一种新型表观遗传甲基化场，可能有助于了解肿瘤微环境的发病机制。为了寻找与食管肿瘤发生有关的基因，我们与 CCR 癌症预防研究分会合作，研究中国山西省高危人群食管鳞状细胞癌 (ESCC) 的分子基础。对有和没有 ESCC 家族史的患者进行等位基因型比较，发现染色体带 13q12 上的一个区域可能含有家族性肿瘤抑制基因。目前正在努力分析感兴趣的基因组区域中的几个候选基因。 I 型多发性内分泌肿瘤 (MEN1) 是一种遗传综合征，其特征是受影响个体中出现神经内分泌肿瘤。该负责基因是由 NIH MEN1 工作组于 1997 年发现的，该工作组包括病理遗传学单位以及来自国家人类基因组研究所、国家生物技术信息中心以及国家糖尿病、消化和肾脏疾病研究所的小组。病理遗传学部门目前的工作包括对人体组织中的 menin 进行免疫组织化学评估。

项目成果

MicroRNA analysis of microdissected normal squamous esophageal epithelium and tumor cells.

• 发表时间: 2011
• 期刊: American journal of cancer research
• 影响因子: 5.3
• 作者: Liang Zhu;Wusheng Yan;J. Rodriguez-Canales;Alex M. Rosenberg;N. Hu;A. Goldstein;P. Taylor;H. Erickso

Decrease in CD8+ lymphocyte number and altered cytokine profile in human prostate cancer.

• 发表时间: 2011
• 期刊: American journal of cancer research
• 影响因子: 5.3
• 作者: G. Gannot;Annely M. Richardson;J. Rodriguez-Canales;P. Pinto;M. Merino;R. Chuaqui;J. Gillespie;M. Emmert-Buck