The FGFR1 Breakapart/Amplification probe consists of a green 272kb probe and a red 267kb probe, which are positioned on each side of the FGFR1 gene. The 8-centromere probe in blue acts as a control for chromosome 8.
Fibroblast Growth Factor Receptor 1 (FGFR1), located on chromosome 8, was the first gene to be shown to be amplified in some breast cancers1 and is also translocated in some patients with 8p11 myeloproliferative syndrome2.
Amplification of the gene is thought to be the causative factor in around 10% of breast tumours3 and has been shown to provide a poor prognosis to patients as over-expression of the gene product can lead to early relapse4.
In common with other genetic defects in lymphoproliferative disorders, like the BCR/ABL translocation in CML, the FGFR1 gene contains sequences that could code for a putative tyrosine kinase protein5,6, which has been implicated in myeloproliferative syndrome (also known as EMS or Stem cell leukaemia/lymphoma syndrome, SCLL), marking out the importance of this gene in both solid tumours and cancers of the blood. There are at least eight partner genes involved with FGFR1 translocations, including ZNF198 (the most common7), FOP, CEP110, BCR, HERV-K, FGFR10P2, TIF1 and MYO18A8.
CytoCell has developed a three-colour combined breakapart and amplification FISH probe for FGFR1 that can be used in either bone marrow samples from myeloproliferative syndrome (EMS) patients or tissue sections from patients where gene amplification may be suspected. In EMS, the breakapart strategy will show the split of one of the two fusion signals along with a blue centromere to enumerate chromosome 8. In patients that are being tested for amplifications of FGFR1, the non-translocated FGFR1 FISH probe will appear as a fusion signal and this will appear amplified. The chromosome 8 centromere probe will also act as a control probe in these cases.