Novak Urban, Tobler Andreas, Fey Martin F
Department of Medical Oncology and Haematology, University and Inselspital Berne, Switzerland.
Leuk Lymphoma. 2004 May;45(5):887-96. doi: 10.1080/1042819032000159843.
B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous malignant disease, both in terms of molecular abnormalities and clinical course. The most frequent chromosomal aberrations in B-CLL are deletions on 13q, 11q, and 17p, and trisomy 12, all of which are of prognostic significance. These aberrations can be detected by conventional cytogenetic analysis and fluorescence in situ hybridization (FISH), but cytogenetics are hampered by the low mitotic index of B-CLL cells, and FISH depends on genetic information of candidate regions. Microsatellites are unique highly polymorphic and informative genetic markers dispersed in the human genome. They have become the most commonly used markers to trace loss of heterozygosity in tumors. Their detection by PCR is rapid and can be semi-automated with maximal robustness and reproducibility. In this review, we discuss the implications of a recent genome-wide analysis in B-CLL with 400 microsatellite markers. This analysis led to the detection of new aberrant loci in B-CLL which are not visible in the leukemic conventional karyotype. We conclude that microsatellite allelotyping provides a complementary comprehensive view of genetic alterations in B-CLL, and it may identify new loci with candidate genes relevant in the molecular biology of B-CLL.
B细胞慢性淋巴细胞白血病（B-CLL）是一种异质性恶性疾病，无论是在分子异常还是临床病程方面。B-CLL中最常见的染色体畸变是13q、11q和17p缺失以及三体12，所有这些都具有预后意义。这些畸变可以通过传统细胞遗传学分析和荧光原位杂交（FISH）检测到，但细胞遗传学受到B-CLL细胞低有丝分裂指数的阻碍，而FISH依赖于候选区域的遗传信息。微卫星是分散在人类基因组中的独特的高度多态性和信息丰富的遗传标记。它们已成为追踪肿瘤杂合性缺失最常用的标记。通过聚合酶链反应（PCR）检测它们快速，并且可以实现最大程度的稳健性和可重复性的半自动操作。在本综述中，我们讨论了最近使用400个微卫星标记对B-CLL进行全基因组分析的意义。该分析导致在B-CLL中检测到白血病常规核型中不可见的新的异常位点。我们得出结论，微卫星等位基因分型提供了B-CLL遗传改变的补充性全面视图，并且它可能识别出与B-CLL分子生物学相关的具有候选基因的新位点。
