Fusion and amplification of two originally non-syntenic chromosomal regions in a mammary carcinoma cell line.
The FLG/FGFRI gene, encoding a receptor for members of the FGF family, is located at 8p11.2-p12. It is amplified, overexpressed, and not grossly rearranged in the MDA-MB-134 breast carcinoma cell line, whereas other genes from the pericentromeric 8p region are not amplified. The FGF4/HSTFI gene, located at 11q13, is also amplified with a substantial portion of the 11q13 region, but is not overexpressed in MDA-MB-134 cells. In this cell line, amplified sequences constitute a large homogeneously staining region (HSR) which is part of a marker chromosome containing chromosome 8 and chromosome 11 sequences. Using probes for the FGF4/HSTFI and the FLG/FGFRI genes in fluorescence chromosomal in situ hybridization, we show that the HSR contains de novo fused and amplified 11q13 and 8p11-p12 sequences associated in a complex structure containing approximately the same number of FGF4 and FGFRI genes. The significance of this genetic abnormality for MDA-MB-134 cells, and for breast carcinogenesis in general, is unknown, but may underlie a particular type of oncogene activation.
Lafage
M
M
Laboratory of Molecular Hematology and Cytogenetics, U.119 INSERM, Marseille, France.
Pedeutour
F
F
Marchetto
S
S
Simonetti
J
J
Prosperi
M T
MT
Gaudray
P
P
Birnbaum
D
D
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure*; D002898:Chromosomes, Human, Pair 8 / Q000648:ultrastructure*; D003360:Cosmids; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D000091344:Filaggrin Proteins; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D005819:Genetic Markers; D009363:Neoplasm Proteins; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors