Molecular Characterization of Leiomyosarcoma and GIST

平滑肌肉瘤和胃肠道间质瘤的分子特征

• 批准号: 7624686
• 负责人: Jan Matt van de Rijn
• 金额: $ 29.21万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-29 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7624686
• 关键词: Affect; Age; Antibodies; Behavior; Benign; Breast Carcinoma; Carcinoma; Categories; Chemistry; Classification; Clinical; Complement; Data; Development; Diagnostic; Disease; Freezing; Gastrointestinal Stromal Tumors; Gender; Gene Expression; Gene Expression Profiling; Genes; Goals; Histologic; Histology; Imatinib; Immunohistochemistry; In Situ Hybridization; Individual; Infertility; Laboratories; Leiomyoma; Lesion; Location; Malignant - descriptor; Malignant Neoplasms; Malignant Smooth Muscle Neoplasm; Molecular; Molecular Analysis; Molecular Profiling; Mutation; Neoplasm Metastasis; Neoplasms; Operative Surgical Procedures; Pathway interactions; Patients; Pharmaceutical Preparations; Prognostic Marker; Race; Radiation; Research Personnel; Resistance; Resistance development; Sampling; Site; Skin; Smooth Muscle Tumor; Soft Tissue Neoplasms; Specimen; Subgroup; System; Time; Tissue Microarray; Uterus; Validation; Variant; base; comparative genomic hybridization; effective therapy; gene discovery; interest; leiomyosarcoma; new therapeutic target; novel; novel diagnostics; programs; research study; response; sarcoma; soft tissue; therapeutic target; tumor; tumor growth; tumorigenic

DESCRIPTION (provided by applicant): Benign soft tissue tumors (STT) and their malignant variants, sarcomas, form a highly heterogeneous group of tumors. To date, most gene expression profiling studies have examined relatively few cases each of several sarcoma types. The best hope for adequate treatment of patients suffering from malignancies lies in the continuing individualization of therapy for a particular patient. The molecular analysis of carcinomas has helped in identifying subgroups of patients that benefit more from one therapy over another. Perhaps the best example of this is found in breast carcinoma, where ER and HER2Neu status were found to be of great significance. More recently, gene array findings highlighting novel subtypes, such as the "basal subtype" give hope that further individualization of therapy is possible. No clear progress in this direction has been made in the field of sarcomas yet and tumors like leiomyosarcoma (LMS) and gastrointestinal stromal tumor (GIST) are treated as amorphous groups of lesions, despite the fact that LMS behaves in a manner that is influenced by the site of origin of this tumor and the fact that different mutations are known to exist in the KIT and PDGFRa genes in GIST that influence response to Imatinib. The objective of this project is to examine many (>100) samples from each tumor type to reach a molecular characterization of the different subsets of tumors that exist within these 2 categories. During the course of this project novel diagnostic and prognostic markers and novel potential therapeutic targets will be identified. Three relatively new technical developments will be used to achieve these goals: gene expression profiling combined with array-based comparative genomic hybridization to identify novel genes of clinical interest, followed by validation and extension of these findings on tissue microarrays analyzed by immunohistochemistry and/or in situ hybridization.

描述（由申请人提供）：良性软组织肿瘤（STT）及其恶性变体肉瘤形成了高度异质的肿瘤。迄今为止，大多数基因表达分析研究已经检查了相对较少的几种肉瘤类型的病例。充分治疗患有恶性肿瘤的患者的最佳希望在于对特定患者的持续个性化治疗。癌的分子分析有助于鉴定患者的亚组，这些患者从一种疗法中受益于另一种疗法。也许最好的例子是在乳腺癌中发现的，那里的ER和HER2NEU身份很重要。最近，基因阵列发现突出了新型亚型，例如“基础亚型”，使人们希望进一步的个性化治疗。在肉瘤领域尚未在这个方向上取得任何明显的进展，诸如平滑肌肉瘤（LMS）和胃肠道脊髓肿瘤（GIST）等肿瘤被视为无定形的病变群，尽管LMS行为行为会受到该肿瘤的响应和kiT的响应影响的方式，但该肿瘤的响应影响了y和PD在y中的响应，而y和p的响应影响了y和kit的范围。伊马替尼。该项目的目的是检查每种肿瘤类型的许多（> 100）样品，以达到这两种类别中存在的不同肿瘤亚集的分子表征。在这个项目的过程中，将确定新颖的诊断和预后标记以及新的潜在治疗靶标。将使用三个相对较新的技术发展来实现这些目标：基因表达分析与基于阵列的比较基因组杂交结合，以识别临床兴趣的新基因，然后验证和扩展这些发现在通过免疫组织化学和/或原位杂交的组织微阵列上进行的这些发现和扩展。