Chromosomal Abnormalities in Myeloma as Detected by FISH

描述(由申请人提供)：这是一项拨款竞争更新申请资金，以进一步研究多发性骨髓瘤(MM)患者，进入东部合作肿瘤组(ECOG)临床试验E9486/E9487和在梅奥诊所看到的潜在患者，通过分子细胞遗传学方法尝试对疾病进行分子分类。这一建议希望在分子水平上将MM分为不同的患者组，具有独特的生物学特性和预后。我们还将进一步研究13号染色体在MM发病机制中的作用。1.利用新诊断的MM患者样本中的间期FISH，我们将对分子细胞遗传学异常进行全面分析，包括：IgH易位及其特定伴侣；IGL-lambda易位；17p13.1(P53)、11q23(ATM)、9p21(p16/INK4)和22q的缺失；以及delta13。通过这些手段，我们希望阐明它们在MM中的临床、预后和生物学意义。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.勾画13号染色体最小缺失区域，以确定肿瘤抑制基因缺失的区域。3.评估纵向标本中含有Delta13的细胞的克隆进化和选择。4.建立delta13在接受大剂量干细胞支持化疗的MM患者中的预后意义，并将其与常规化疗对MM患者生存的影响进行比较。

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.