Popescu N C, Zimonjic D B
Molecular Cytogenetics Section, National Cancer Institute, Bethesda, Maryland 20892, USA.
Cancer Genet Cytogenet. 1997 Jan;93(1):10-21. doi: 10.1016/s0165-4608(96)00262-2.
Chromosomal abnormalities are the hallmark of cancer cells. Recurring and highly consistent structural and numerical alterations have been identified in a large number of leukemias, lymphomas, and solid tumors. The identification of recurrent genetic alterations and the isolation of molecular markers have clinical applications in the diagnosis and prognosis of neoplasia and in the detection of minimal residual disease that are essential for designing the most effective therapeutic approach. Polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) are powerful techniques for detection of genomic alterations. The battery of FISH methods and DNA probes that are available can resolve virtually any chromosomal alterations regardless of their complexity. Combined chromosome banding, multifluor or spectral karyotype, and comparative genomic hybridization (CGH) allow identification of structural and numerical alterations on a global basis, mapping of the DNA copy number on the entire tumor genome, complete derivation of complex rearrangements, and localization of the breakpoints of translocations and deletions. Regions of recurrent alterations can be microdisected, amplified, microclone libraries constructed and probes localized on extended chromosomes or chromatin fibers for construction of high resolution physical maps that are critical for positional cloning and gene identification. In this review we attempted to cover the current trends in cancer molecular cytogenetics, and to outline the importance of molecular chromosome analysis in the understanding of oncogenesis and its clinical applications.
染色体异常是癌细胞的标志。在大量白血病、淋巴瘤和实体瘤中已发现反复出现且高度一致的结构和数量改变。复发性基因改变的鉴定以及分子标志物的分离在肿瘤的诊断和预后以及微小残留病的检测中具有临床应用价值，而这些对于设计最有效的治疗方法至关重要。聚合酶链反应（PCR）和荧光原位杂交（FISH）是检测基因组改变的强大技术。现有的一系列FISH方法和DNA探针几乎可以解析任何染色体改变，无论其复杂性如何。联合染色体显带、多荧光或光谱核型分析以及比较基因组杂交（CGH）能够在整体水平上鉴定结构和数量改变，绘制整个肿瘤基因组上的DNA拷贝数图谱，完整推导复杂重排以及定位易位和缺失的断点。可以对反复出现改变的区域进行显微切割、扩增，构建微克隆文库，并将探针定位在延伸的染色体或染色质纤维上，以构建高分辨率物理图谱，这对于定位克隆和基因鉴定至关重要。在本综述中，我们试图涵盖癌症分子细胞遗传学的当前趋势，并概述分子染色体分析在理解肿瘤发生及其临床应用中的重要性。
