Rosenberg Carla, Geelen Eric, IJszenga Marije J, Pearson Peter, Tanke Hans J, Dinjens Winand N M, van Dekken Herman
Laboratory of Cytochemistry and Cytometry, Department Molecular Cell Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
Cancer Genet Cytogenet. 2002 May;135(1):35-41. doi: 10.1016/s0165-4608(01)00639-2.
Adenocarcinomas arising around the gastro-esophageal junction (GEJ) are highly malignant, and their incidence has risen rapidly in the last decades. Cell lines are the basic in vitro system for functional and therapeutic studies in GEJ tumors, but only a small number of cell lines are currently available, and none of them has been fully karyotyped. We analyzed 5 GEJ tumor cell lines using a combination of 24-color fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH) and genomic microarrays. Using CGH we demonstrated that these cell lines present imbalances similar to those we had previously observed in primary GEJ tumors, namely gains on 1q, 7q, 8q, 17q, 19q, 20, and X, and losses on 3p, 4, 5q, 9p, 18q, and 21. Multicolor FISH karyotyping revealed multiple structural rearrangements involving chromosomes 1, 5, 6, 7, 8, 9, 13, 17, 18, and 22. Rearrangements of chromosome 8 involved 10 different chromosomes, while rearrangements of chromosome 17 involved 5. Different rearrangements resulted in imbalances of similar chromosome regions, suggesting that similar genomic imbalances are constitutively important but are achieved through different pathways. The use of a commercially available genomic array excluded TOP2A (17q), and MYBL2, PTPT1, CSE1L, and ZNF217 (20q) as candidate genes for frequently amplified areas on these chromosomes, and contributed to refining the limits of chromosome regions involved in genomic imbalances.
胃食管交界（GEJ）周围发生的腺癌恶性程度高，在过去几十年中其发病率迅速上升。细胞系是GEJ肿瘤功能和治疗研究的基本体外系统，但目前仅有少数细胞系可用，且均未进行全面的核型分析。我们结合使用24色荧光原位杂交（FISH）、比较基因组杂交（CGH）和基因组微阵列分析了5种GEJ肿瘤细胞系。通过CGH我们证明，这些细胞系存在与我们之前在原发性GEJ肿瘤中观察到的类似的失衡，即1q、7q、8q、17q、19q、20和X染色体的增益，以及3p、4、5q、9p、18q和21染色体的缺失。多色FISH核型分析揭示了涉及1、5、6、7、8、9、13、17、18和22号染色体的多种结构重排。8号染色体的重排涉及10条不同的染色体，而17号染色体的重排涉及5条。不同的重排导致相似染色体区域的失衡，这表明相似的基因组失衡在本质上很重要，但通过不同的途径实现。使用市售的基因组阵列排除了TOP2A（17q）以及MYBL2、PTPT1、CSE1L和ZNF217（20q）作为这些染色体上频繁扩增区域的候选基因，并有助于细化涉及基因组失衡的染色体区域的界限。
