Clinical implication of genome-wide profiling in diffuse large B-cell lymphoma and other subtypes of B-cell lymphoma.

Clinical implication of genome-wide profiling in diffuse large B-cell lymphoma and other subtypes of B-cell lymphoma.
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DOI:
10.4103/0019-509x.35814
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发表时间:
2007-04
影响因子:
1
通讯作者:
J. Iqbal;S. Joshi;K. Patel;Sofi I Javed;C. Kűcűk;Afeera Aabida;F. d'Amore;K. Fu
J. Iqbal;S. Joshi;K. Patel;Sofi I Javed;C. Kűcűk;Afeera Aabida;F. d'Amore;K. Fu
中科院分区:
医学4区
文献类型:
--
作者:
J. Iqbal;S. Joshi;K. Patel;Sofi I Javed;C. Kűcűk;Afeera Aabida;F. d'Amore;K. Fu

文献摘要

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淋巴样细胞的分化在其发育的不同阶段受到转录因子的严格调控。在成熟过程中,可能发生不同的基因组改变或畸变,如染色体易位、突变和缺失,最终可能导致不同的生物学和临床肿瘤。不同的分化阶段导致淋巴恶性肿瘤的异质性,这可能会使诊断变得复杂。淋巴系统疾病的最初诊断方案是由Rappaport提出的,随后是修订的欧洲和美国类淋巴瘤分类(真实的)和世界卫生组织(WHO)分类。这些分类方法基于组织学、免疫表型和细胞遗传学标记,并被世界各地的病理学家和肿瘤学家广泛接受。在过去的几十年里,对恶性淋巴瘤的病因、发病机制和分子生物学的研究取得了很大进展。然而,淋巴瘤发生的分子机制的详细知识在很大程度上是未知的。基于新分类的新治疗方案已在临床试验中,但收效甚微。因此,在分子水平上了解肿瘤的基本生物学是必要的。一种重要的方法是测量肿瘤基因组的活性,这可以部分地通过测量整个细胞的mRNA来实现。进行高通量分析的关键技术之一是DNA微阵列技术。全基因组转录水平的测量,也称为基因表达谱(GEP),可以准确地确定肿瘤的生物学表型。在这篇综述中,全基因组GEP在了解淋巴瘤生物学方面的重要发现以及微阵列的诊断和预后价值进行了讨论。
The differentiation of lymphoid cells is tightly regulated by transcription factors at various stages during their development. During the maturation processes, different genomic alterations or aberrations such as chromosomal translocation, mutation and deletions may occur that can eventually result in distinct biological and clinical tumors. The different differentiation stages create heterogeneity in lymphoid malignancies, which can complicate the diagnosis. The initial diagnostic scheme for lymphoid diseases was coined by Rappaport followed by Revised European and American Classification of Lymphoid Neoplasms (REAL) and World Health Organization (WHO) classifications. These classification methods were based on histological, immunophenotypic and cytogenetic markers and widely accepted by pathologists and oncologists worldwide. During last several decades, great progress has been made in understanding the etiology, pathogenesis and molecular biology of malignant lymphoma. However, detailed knowledge in the molecular mechanism of lymphomagenesis is largely unknown. New therapeutic protocols based on the new classification have been on clinical trials, but with little success. Therefore, it is imperative to understand the basic biology of the tumor at molecular level. One important approach will be to measure the activity of the tumor genome and this can partly be achieved by the measurement of whole cellular mRNA. One of the key technologies to perform a high-throughput analysis is DNA microarray technology. The genome-wide transcriptional measurement, also called gene expression profile (GEP) can accurately define the biological phenotype of the tumor. In this review, important discoveries made by genome-wide GEP in understanding the biology of lymphoma and additionally the diagnostic and prognostic value of microarrays are discussed.