Thiagalingam S, Lengauer C, Leach F S, Schutte M, Hahn S A, Overhauser J, Willson J K, Markowitz S, Hamilton S R, Kern S E, Kinzler K W, Vogelstein B
Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
Nat Genet. 1996 Jul;13(3):343-6. doi: 10.1038/ng0796-343.
Chromosome deletions are the most common genetic events observed in cancer. These deletions are generally thought to reflect the existence of a tumour suppressor gene within the lost region. However, when the lost region does not precisely coincide with a hereditary cancer locus, identification of the putative tumour suppressor gene (target of the deletion) can be problematic. For example, previous studies have demonstrated that chromosome 18q is lost in over 60% of colorectal as well as in other cancers, but the lost region could not be precisely determined. Here we present a rigorous strategy for mapping and evaluating allelic deletions in sporadic tumours, and apply it to the evaluation of chromosome 18 in colorectal cancers. Using this approach, we define a minimally lost region (MLR) on chromosome 18q21, which contains at least two candidate tumour suppressor genes, DPC4 and DCC. The analysis further suggested genetic heterogeneity, with DPC4 the deletion target in up to a third of the cases and DCC or a neighbouring gene the target in the remaining tumours.
染色体缺失是癌症中最常见的基因事件。这些缺失通常被认为反映了缺失区域内存在肿瘤抑制基因。然而，当缺失区域与遗传性癌症位点不完全一致时，鉴定假定的肿瘤抑制基因（缺失的靶点）可能会有问题。例如，先前的研究表明，超过60%的结直肠癌以及其他癌症中存在18号染色体q臂缺失，但无法精确确定缺失区域。在此，我们提出了一种用于绘制和评估散发性肿瘤中等位基因缺失的严谨策略，并将其应用于评估结直肠癌中的18号染色体。使用这种方法，我们在18号染色体q21上定义了一个最小缺失区域（MLR），该区域至少包含两个候选肿瘤抑制基因DPC4和DCC。分析进一步表明存在基因异质性，在多达三分之一的病例中，DPC4是缺失靶点，而在其余肿瘤中，DCC或其邻近基因是靶点。
