Chromosomal Abnormalities in Myeloma as Detected by FISH

描述（由申请人提供）：这是一项竞争性续期拨款申请，申请资金用于进一步研究多发性骨髓瘤（MM）患者，这些患者已进入东部肿瘤合作小组（ECOG）临床试验E9486/E9487，以及在梅奥诊所就诊的前瞻性患者，通过分子细胞遗传学方法尝试对该疾病进行分子分类。该建议希望在分子水平上将MM分类为具有独特生物学和预后的离散组。我们还将进一步研究13号染色体在MM发病机制中的作用。在新诊断的MM患者样本中使用间期FISH，我们将对分子细胞遗传学异常进行全面分析，包括：IgH易位及其特定伙伴；IgL-lambda易位;17p13.1 （p53）、11q23 （ATM）、9p21 （p16/INK4）和22q缺失；和delta13。通过这些方法，我们希望阐明它们在MM中的临床、预后和生物学重要性。我们将在进入ECOG III期临床试验E9486和相关实验室研究E9487的MM患者中检测这些异常。2. 描绘13号染色体的最小缺失区域，以确定提示肿瘤抑制基因缺失的区域。3. 在纵向获得的样本中评估含delta13细胞的克隆进化和选择。4. 建立delta13在接受干细胞支持的大剂量化疗的MM患者中的预后意义，并将其与delta13对接受常规化疗的MM患者生存的影响进行对比。

DESCRIPTION (provided by applicant): This is a grant competitive renewal requesting funding to further study multiple myeloma (MM) in patients, entered into the Eastern Cooperative Oncology Group (ECOG) clinical trials E9486/E9487 and prospective patients seen at the Mayo Clinic, by molecular cytogenetic methods to attempt a molecular classification of the disease. This proposal hopes to classify MM at a molecular level into discrete groups of patients with unique biology and prognosis. We will also further study the role chromosome 13 plays in the pathogenesis of MM. Specific Aims 1. Using interphase FISH in newly diagnosed MM patient samples we will perform a comprehensive analysis of molecular cytogenetic abnormalities, including: IgH translocations and their specific partners; IgL-lambda translocations; deletions of 17p13.1 (p53), 11q23 (ATM), 9p21 (p16/INK4), and 22q; and delta13. By these means, we hope to elucidate their clinical, prognostic and biological importance in MM. We will test for these abnormalities in MM patients entered into the ECOG Phase III clinical trial E9486 and associated correlative laboratory study E9487. 2. To delineate a minimally deleted region of chromosome 13 to identify area suggestive of tumor suppressor gene deletions. 3. To assess for clonal evolution and selection of delta13 containing cells in longitudinally obtained samples. 4. To establish the prognostic significance of delta13 in MM patients undergoing high-dose chemotherapy with stem cell support and contrast this to the effect of delta13 on survival in MM patients treated with conventional chemotherapy.