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IGH 及其片段的缺失与 t(11;14)(q13;q32)多发性骨髓瘤中 13q14 缺失的相关性。

Correlation between losses of IGH or its segments and deletions of 13q14 in t(11;14) (q13;q32) multiple myeloma.

机构信息

Division of Hematology and the Sheba Cancer Research Center, The Chaim Sheba Medical Center, Tel-Hashomer, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

出版信息

Genes Chromosomes Cancer. 2010 Jan;49(1):17-27. doi: 10.1002/gcc.20716.

Abstract

Multiple myeloma (MM) is a malignancy of the plasma cells (PCs) characterized by a wide variety of genetic and chromosomal abnormalities. In recent years, major attention was drawn to the significance of chromosomal aberrations involving chromosome arm 13q and the IGH region on chromosome band 14q32 as a prognostic indicator in MM. In this study we applied a combined cell morphology and FISH method for the analysis of coexistence of t(11;14)(q13;q32) with deletions of the long arm of chromosome 13 (Delta13) in PCs from 51 MM patients using several probes for the 13q14, 11q13, and IGH regions. We found 15 different variants of the t(11;14) that are the consequence of different 11q13 breakpoints and various deletions of Variable (del IGH Var) or Constant (del IGH Const) IGH segments and also duplications and losses of the IGH gene on the normal nontranslocated chromosome 14 as well as IGH/Cyclin D1 (CCND1) fusion on der(14) and CCND1/IGH fusions on der(11). A strong association between Delta13 and specific variants of t(11;14) was found: variants with deletion of the IGH gene or its segments were found only in MM cases with deleted chromosome 13, while the common translocation t(11;14) was found only in the MM cases with normal chromosome arm 13q. In contrast, we did not find any association between Delta13 and deletions of the IGH gene or its segments in the MM patients with t(4;14)(p16;q32).

摘要

多发性骨髓瘤(MM)是一种浆细胞(PC)恶性肿瘤,其特征是存在广泛的遗传和染色体异常。近年来,人们主要关注涉及 13 号染色体臂和 14 号染色体带 14q32 上 IGH 区的染色体畸变作为 MM 预后指标的意义。在这项研究中,我们应用细胞形态学和 FISH 联合方法,使用针对 13q14、11q13 和 IGH 区域的多个探针,分析了 51 例 MM 患者 PC 中 t(11;14)(q13;q32)与 13 号染色体长臂缺失(Delta13)共存的情况。我们发现了 15 种不同的 t(11;14)变体,这些变体是不同的 11q13 断裂点和可变(del IGH Var)或恒定(del IGH Const)IGH 片段的各种缺失以及正常非易位染色体 14 上 IGH 基因的重复和缺失以及 der(14)上的 IGH/Cyclin D1(CCND1)融合和 der(11)上的 CCND1/IGH 融合的结果。我们发现 Delta13 与特定的 t(11;14)变体之间存在很强的关联:缺失 IGH 基因或其片段的变体仅在缺失 13 号染色体的 MM 病例中发现,而常见的易位 t(11;14)仅在 13q 号染色体正常的 MM 病例中发现。相比之下,我们在具有 t(4;14)(p16;q32)的 MM 患者中没有发现 Delta13 与 IGH 基因或其片段缺失之间的任何关联。

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