Classification of ambiguous melanocytic tumors

不明确的黑素细胞肿瘤的分类

• 批准号: 6663286
• 负责人: Boris C. Bastian
• 金额: $ 31.96万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-25 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6663286
• 关键词: biomarker; chromosome aberrations; clinical research; comparative genomic hybridization; computer program /software; diagnosis design /evaluation; fluorescent in situ hybridization; genetic markers; histopathology; human tissue; melanoma; metastasis; microarray technology; neoplasm /cancer classification /staging; neoplasm /cancer diagnosis; neoplasm /cancer genetics; prognosis

DESCRIPTION (provided by applicant) While current histopathological criteria permit classifying the majority of melanocytic tumors as either benign nevi or melanoma, well-documented uncertainty exists in a significant number of cases. Misclassification results in inappropriate over- or under-treatment of patients. Our recent work using comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) on primary tumors has shown that the pattern of genomic aberrations differs significantly between clearly identifiable melanoma and benign nevi. The vast majority of primary melanomas have multiple chromosomal aberrations, whereas the vast majority of nevi do not have any. The few benign nevi that do have aberrations typically have a very restricted set, which does not occur in melanoma. This project will determine if a similar genomic analysis would help distinguish between benign and malignant lesions that are ambiguous by current histopathological criteria, and if those morphological criteria can be improved. In this project we will use two separate cohorts of histologically ambiguous melanocytic tumors that have extensive follow-up in order to systematically screen for genomic and histopathological markers that can predict outcome. The first cohort will serve as a training set and the second as a test set for validation. Cases will be contributed by a panel of internationally recognized pathologists with great expertise in melanocytic tumors. The genomic analysis will take advantage of array-based CGH. This technology has recently been developed in our laboratories and provides a resolution of approximately 1 megabase across the human genome. This technique can be performed with small amounts of DNA extracted from routinely fixed archival tissue from primary tumors. First, we will use array CGH on the training set to screen for genomic aberrations that distinguish metastasizing and non-metastasizing cases and the expert panel will use these same tumors to develop improved morphological classification criteria. The genetic and morphological criteria will be built into classification rules using the training set. The vies that work best on the training set will be validated on the independent set of tumors. Finally, we will implement the genomic rule in form of hybridization probes for a few specific loci and develop a FISH-based test. The long-term goals of this project are to find genetic and morphological criteria that can classify melanocytic tumors that are low ambiguous and to develop a prototype clinical test for this purpose. Such a test would be of significant clinical relevance, as it would help to identify patients who need additional treatment, and prevent others from getting inappropriately aggressive treatment. In addition, this project will provide a detailed view of the aberrations found in melanocytic tumors, their prevalence and prognostic relevance.

描述（由申请人提供） 虽然目前的组织病理学标准允许对大多数 黑素细胞肿瘤为良性痣或黑色素瘤，有据可查 在很多情况下都存在不确定性。错误分类结果 对患者的不当过度或治疗不足。我们最近的工作使用 比较基因组杂交（CGH）和荧光原位杂交 （FISH）对原发性肿瘤的研究表明，基因组畸变的模式 可清晰识别的黑色素瘤和良性痣之间存在显着差异。 绝大多数原发性黑色素瘤具有多种染色体畸变， 而绝大多数痣都没有。少数良性痣会这样做 像差通常有一个非常有限的集合，这不会发生在 黑色素瘤。该项目将确定类似的基因组分析是否有帮助 区分当前模糊的良性和恶性病变 组织病理学标准，如果这些形态学标准可以 改善了。在这个项目中，我们将使用两个独立的组织学队列 不明确的黑素细胞肿瘤需要进行广泛的随访，以便 系统地筛选基因组和组织病理学标记物 预测结果。第一个队列将作为训练集，第二个队列将作为训练集 作为验证的测试集。案件将由一个小组提供 国际公认的病理学家，在黑素细胞方面拥有丰富的专业知识 肿瘤。基因组分析将利用基于阵列的 CGH。这 我们的实验室最近开发了技术，并提供了 整个人类基因组的分辨率约为 1 兆碱基。这种技术 可以用从常规固定中提取的少量 DNA 进行 来自原发肿瘤的档案组织。首先，我们将在 用于筛选区分转移的基因组畸变的训练集 和非转移病例，专家小组将使用这些相同的肿瘤来 制定改进的形态学分类标准。遗传和 形态标准将被构建到分类规则中，使用 训练集。在训练集上效果最好的比赛将在 独立的一组肿瘤。最后，我们将实施基因组规则 针对一些特定位点的杂交探针形式，并开发基于 FISH 的探针 测试。该项目的长期目标是寻找遗传和 可以对低黑色素细胞肿瘤进行分类的形态学标准 模糊性并为此目的开发原型临床测试。这样一个 测试将具有重要的临床意义，因为它有助于识别 需要额外治疗的患者，并阻止其他人接受 不适当的积极治疗。此外，该项目将提供黑色素细胞肿瘤中发现的畸变、其患病率和预后相关性的详细视图。