CCND1 and FGFR1 coamplification results in the colocalization of 11q13 and 8p12 sequences in breast tumor nuclei.
The CCND1 gene, localized to chromosome band 11q13, is amplified in approximately 15% of human primary breast tumors. From 30 to 40% of the tumors presenting this amplification show concomitant amplification at the FGFR1 locus in 8p12. Similarly, MDA-MB-134 breast cancer cells bear CCND1 and FGFR1 coamplified, resulting in the formation of a hybrid intrachromosomal amplification assembling 11q13 and 8p12 sequences. To learn whether similar amplified structures arise in breast tumors, we used a two-color FISH approach on interphase nuclei. A cohort of 225 breast tumors was analyzed by Southern blotting and a subset of 12 tumors presenting the 11q13-8p12 coamplification was selected for further study by interphase FISH. In 6/12 tumors the FISH signals for 11q13 and 8p12 probes formed colocalizing clusters of green and red spots in the nuclei. The FISH patterns were identical to those observed on MDA-MB-134 interphase nuclei hybridized with 11q13 and 8p12. These data, suggesting the formation in these tumors of a hybrid amplification domain in which 11q13 and 8p12 sequences are joined, were reinforced by dual-color FISH on extended chromatin showing that the said were sequentially aligned in these tumors. Furthermore, 3/6 nuclei with colocalized 11q13 and 8p12 amplifications showed fusion of centromeric sequences from chromosomes 8 and 11. Our data strongly suggest the occurrence, in approximately 3% of primary breast tumors, of a recurrent rearrangement involving the proximal portions of 8p and 11q and resulting in the formation of a hybrid amplified structure composed of 11q13 and 8p12 sequences.
Institut de Génétique Moléculaire, UMR 5535 du CNRS and Centre de Recherche en Cancérologie, CRLC Val d'Aurelle-Paul Lamarque, Montpellier, France.
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D001483:Base Sequence; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002467:Cell Nucleus / Q000235:genetics*; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics*; D005784:Gene Amplification / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D021141:Nucleic Acid Amplification Techniques; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D014407:Tumor Cells, Cultured
D017468:Receptors, Fibroblast Growth Factor; D019938:Cyclin D1; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1