FGFR1, 8p11.2 Rearrangement, FISH
Aids in identifying patients with myeloproliferative syndromes and the t(8;var)(p11.2;var) translocation who therefore are likely resistant to current chemotherapies
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The gene for fibroblast growth factor receptor 1 (FGFR1) is located at 8p11.2 and rearrangements of FGFR1 are found in stem cell myeloproliferative disorders involving both lymphoid and myeloid lineages. The stem cell myeloproliferative disorders with FGFR1 rearrangements are also called 8p11 (eight p11) myeloproliferative syndromes (EMS) and have variable presentations. EMS often transform rapidly into myelomonocytic leukemia and generally have a poor outcome due to resistance to current chemotherapies, including imatinib; median survival is about 12 months.
All translocations affecting FGFR1 have a similar structure with a 5' gene partner translocating to the 3' FGFR1 at exon 9. The fusion transcripts encode large proteins containing the N-terminus of the translocation partner, and the tyrosine kinase domain of FGFR1 in the C-terminus. Leukemogenesis is caused by inappropriate activation of FGFR1.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal cutoff for any given probe.
The presence of a positive clone supports a diagnosis of malignancy.
The absence of an abnormal clone does not rule out the presence of neoplastic disorder.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not approved by the FDA and it is best used as an adjunct to existing clinical and pathologic information.
A blinded study using the FGFR1 break-apart probe set was performed on 44 fixed cell pellets from blood and bone marrow specimens, 19 patients with t(8p11.2;var) by chromosome analysis and 25 normal control specimens. Rearrangement of FGFR1 was identified in 17 of 19 neoplastic specimens. The FGFR1 gene rearrangement was not detected in any of the 25 control specimens. The normal controls were used to generate a normal cutoff for this assay.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Huret JL: FGFR1 (fibroblast growth factor receptor 1). Atlas Genet Cytogenet Oncol Haematol December 2008, Available from URL: http://AtlasGeneticsOncology.org/Genes/FGFR1113.html Accessed 4/6/2011
2. Patnaik MM, Gangat N, Knudson RA, et al: Chromosome 8p11.2 translocations: prevalence, FISH analysis for FGFR1 and MYST3, and clinicopathologic correlates in a consecutive cohort of 13 cases from a single institution. Am J Hematol 2010;85:238-242
3. WHO Classification of Tumours of Hematopoietic and Lymphoid Tissues. Edited by SH Swerdlow, E Campo, NL Harris, et al. Published by the International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69372 Lyon Cedex 08, France, 2008, pp 72-73