CORRELATIVE STUDIES USING SPECIMENS FROM SWOG 9321

描述（改编自研究者摘要）：细胞遗传学研究 由阿肯色州医学科学大学的骨髓瘤研究小组 （UAMS）作为1,000多名患者临床分期的一部分， 发现染色体13（c13）的部分或完全缺失， 与严重的预后相关，即使是串联自体移植， 其他强有力的预后变量的临床意义，如 β 2微球蛋白和C反应蛋白的多变量分析。最近 研究应用分子分析，如比较基因组 杂交和荧光原位杂交（FISH）显示c13 在高达50%的患者中缺失，而G显带中为15%至20%。 重要的是，RB缺失与较短的无事件和总体 生存率，代表100例患者的单一最不利特征 接受标准化疗 c13缺失的严重后果与一个或多个基因的缺失是一致的。 骨髓瘤肿瘤抑制基因。审查145名G-带 c13缺失的骨髓瘤核型显示，13 q14带可能是骨髓瘤的一个染色体异常。 假定的肿瘤抑制基因的位点，因为这条带是最小的（？） 删除区域，并涉及>90%的情况。三色间期FISH 39例骨髓瘤的分子探针分析 C13的臂鉴定了几个缺失热点，2个在13 q14，1个在13 q21。 为了证实这些结果，并对13 q进行更全面的分析， 进入SWOG 9321的骨髓瘤患者的缺失频率，间期FISH 用一组特异于这些分子缺失热点的分子探针 将进行广泛的统计分析， 发现c13缺失频率和模式的真实发生率， C13基因缺失与预后关系最密切。 UAMS作为所有骨髓活检的中央储存库， 组间试验（>600例患者），进行组织学评价（Bartl 分级）以确定预后对结果的影响。使用新技术 开发用于对石蜡包埋的骨髓活检进行FISH分析 材料，一个前所未有的机会存在，应用国家的最先进的 本试验中存档的骨[骨髓]标本的分子技术，以及 在首席统计师的努力下， 进行跨组试验 提出了三个目标。具体目标1：确定真实发生率， 骨髓瘤患者骨髓活检中c13缺失的模式 在SWOG 9321中登记使用三色间期FISH。具体目标二： 确定13号染色体缺失与标准预后 指标具体目标3：评估13号染色体缺失是否与 临床结果（完全缓解、无事件生存期和总体 生存）。

DESCRIPTION (As Adapted from the Investigator's Abstract): Cytogenetic studies by the myeloma research team at the University of Arkansas for Medical Sciences (UAMS) as part of the clinical staging of more than 1,000 patients has led to the discovery that partial or complete deletions of chromosome 13 (c13) are associated with a grave prognosis even with tandem autotransplants, exceeding the clinical implications of other powerful prognostic variables, such as beta-2 microglobulin and C-reactive protein on multivariate analyses. Recent investigations applying molecular analyses such a comparative genomic hybridization and fluorescence in situ hybridization (FISH) have shown c13 deletions in up to 50% of patients, compared to 15% to 20% in G-banding. Importantly, RB deletion was associated with shorter event free and overall survival, representing the single most adverse feature in 100 patients receiving standard chemotherapy. The grave consequences of c13 deletion is consistent with loss of one or more myeloma tumor suppressor genes on this chromosome. Review of 145 G-banded myeloma karyotypes with c13 deletions revealed that band 13q14 is the likely site of the putative tumor suppressor gene, as this band is the minimally (???) deleted region and invovled in >90% of the cases. Triple-color interphase FISH analysis on 39 myeloma patients with a panel of molecular probes spanning the q arm of c13 has identified several deletion hotspots, 2 at 13q14 and 1 at 13q21. To confirm these results and to perform a more comprehensive analysis of 13q deletion frequencies of myeloma patients entering SWOG 9321, interphase FISH with a panel of molecular probes specific for these molecular deletion hotspots will be conducted and extensive statistical analyses will be performed to discover the true incidence of c13 deletion frequency and patterns and whether c13 deletion is the most relevant correlate with prognosis in this disease. UAMS serves as the central repository for all bone marrow biopsies from this intergroup trial (>600 patients), performing histological evaluation (Bartl Grading) to determine prognostic implications for outcome. Using new techniques developed to perform FISH analyses on paraffin-embedded bone marrow biopsy material, an unprecedented opportunity exists to apply state-of-the art molecular technology to archived bone [marrow] specimens from this trial, and to correlate findings and prognosis, with the efforts of the Chief Statistician for this intergroup trial. Three aims are proposed. Specific Aim 1: Determine the true incidence and pattern of c13 deletions in bone marrow biopsies from patients with myeloma enrolled in SWOG 9321 using triple color interphase FISH. Specific Aim 2: Determine the relationship of chromosome 13 deletions to standard prognostic indicators. Specific Aim 3: Evaluate whether chromosome 13 deletions correlate with clinical outcome (complete remission, event free survival, and overall survival).