Biomarkers for the Early Detection of Pancreatic Cancer

用于早期检测胰腺癌的生物标志物

• 批准号: 7109407
• 负责人: ANN M KILLARY
• 金额: $ 58.49万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-28 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7109407
• 关键词: biomarker; cancer registry /resource; clinical research; cooperative study; early diagnosis; fluorescent in situ hybridization; functional /structural genomics; gene expression profiling; genetic mapping; genetic markers; human genetic material tag; human tissue; neoplasm /cancer diagnosis; neoplasm /cancer genetics; oncogenes; pancreas neoplasms; single nucleotide polymorphism; tumor suppressor genes

DESCRIPTION (originally provided by applicant): Identification of genetic changes associated with the development of intraepithelial ductal neoplasia and those correlating with progression to invasive cancer are expected to provide important clues on the genetic mechanisms causing malignant transformation and progression processes. Such investigations should help develop novel markers for early detection of intraepithelial lesions and those predisposed to progress to invasive cancer. We are proposing to pursue genomics and molecular genetics based approaches to characterize putative target loci on selected specific individual chromosomes, frequently implicated in pancreatic cancer, which harbor genes deleted ("loss of function tumor suppressor genes") and over expressed in pancreatic cancer ("gain of function oncogenes"). Additionally, we are also proposing to do genome wide microsatellite instability, methylation assays and expression profiling studies between paired normal and tumor samples to identify genetic anomalies associated with initiation and progression of pancreatic cancer. The overall goal of this project is to identify early detection genetic biomarkers for pancreatic cancer with an integrated approach of molecular genetic, genomic array and expression array analyses of tumor tissues, serum and pancreatic juice from pancreatic cancer patients. The chromosomal loci to be studied will include the target tumor suppressor gene(s) harboring chromosomes lp and 3p and minimally amplified regions harboring putative oncogenes on chromosomes 20q and 12p. We hypothesize that pathways involving tumor suppressor genes with loss of function mutations/deletions and dominantly activated/amplified/ over-expressed oncogenes are critical determinants in the development of early phases of pancreatic neoplasia. From these loci, we will be developing locus specific DNA based fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR) assays and also protein specific immunochemical detection assays for early detection of intraepithelial pancreatic neoplasia.

描述（最初由申请人提供）：与上皮内导管瘤形成相关的遗传变化以及与侵袭性癌症进展相关的遗传变化的鉴定预计将为导致恶性转化和进展过程的遗传机制提供重要线索。 此类研究应有助于开发新的标记物，用于早期检测上皮内病变和易于进展为浸润性癌症的病变。我们建议采用基于基因组学和分子遗传学的方法来表征选定的特定个体染色体上的假定目标位点，这些位点通常与胰腺癌有关，这些基因座含有删除的基因（“功能丧失的肿瘤抑制基因”）和在胰腺癌中过度表达的基因（“功能获得癌基因”）。此外，我们还建议在配对的正常和肿瘤样本之间进行全基因组微卫星不稳定性、甲基化测定和表达谱研究，以识别与胰腺癌发生和进展相关的遗传异常。 该项目的总体目标是通过对胰腺癌患者的肿瘤组织、血清和胰液进行分子遗传学、基因组阵列和表达阵列分析的综合方法来确定胰腺癌的早期检测遗传生物标志物。要研究的染色体基因座将包括含有1p和3p染色体的靶肿瘤抑制基因以及20q和12p染色体上含有推定癌基因的最小扩增区域。 我们假设涉及具有功能缺失突变/缺失的肿瘤抑制基因和显性激活/扩增/过度表达的癌基因的通路是胰腺肿瘤早期发展的关键决定因素。 根据这些位点，我们将开发基于位点特异性 DNA 的荧光原位杂交 (FISH) 和聚合酶链反应 (PCR) 测定以及蛋白质特异性免疫化学检测测定，以早期检测上皮内胰腺肿瘤。