Spectrum of genetic changes in gastro-esophageal cancer cell lines determined by an integrated molecular cytogenetic approach.
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.
Rosenberg
Carla
C
Laboratory of Cytochemistry and Cytometry, Department Molecular Cell Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands. c.rosenberg@lumc.nl
Geelen
Eric
E
IJszenga
Marije J
MJ
Pearson
Peter
P
Tanke
Hans J
HJ
Dinjens
Winand N M
WN
van Dekken
Herman
H
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000782:Aneuploidy; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics* / Q000648:ultrastructure; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology*; D005784:Gene Amplification; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins