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Identification of four new translocations involving FGFR1 in myeloid disorders
Author(s) -
Sohal Jastinder,
Chase Andrew,
Mould Sarah,
Corcoran Martin,
Oscier David,
Iqbal Sameena,
Parker Sally,
Welborn Jeanna,
Harris Richard I.,
Martinelli Giovanni,
Montefusco Vittorio,
Sinclair Paul,
Wilkins Bridget S.,
van den Berg Henk,
Vanstraelen Danny,
Goldman John M.,
Cross Nicholas C.P.
Publication year - 2001
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.1177
Subject(s) - exon , chromosomal translocation , myeloid leukemia , biology , breakpoint , karyotype , myeloid , microbiology and biotechnology , fibroblast growth factor receptor 1 , myeloproliferative disorders , cancer research , genetics , gene , immunology , chromosome , receptor , fibroblast growth factor
The 8p11 myeloproliferative syndrome (EMS) is associated with three translocations, t(8;13)(p11;q12), t(8;9)(p11;q33), and t(6;8)(q27;p11), that fuse unrelated genes ( ZNF198, CEP110, and FOP , respectively) to the entire tyrosine kinase domain of FGFR1 . In all cases thus far examined (n = 10), the t(8;13) results in an identical mRNA fusion between ZNF198 exon 17 and FGFR1 exon 9. To determine if consistent fusions are also seen in the variant translocations, we performed RT‐PCR on four cases and sequenced the products. For two patients with a t(8;9), we found that CEP110 exon 15 was fused to FGFR1 exon 9. For two patients with a t(6;8), we found that FOP exon 5 (n = 1) or exon 7 (n = 1) was fused to FGFR1 exon 9. To determine if FGFR1 might be involved in other myeloid disorders with translocations of 8p, we developed a two‐color FISH assay using two differentially labeled PAC clones that flank FGFR1 . Disruption of this gene was indicated in a patient with a t(8;17)(p11;q25) and Ph‐negative chronic myeloid leukemia in association with systemic malignant mast cell disease, a patient with acute myeloid leukemia with a t(8;11)(p11;p15), and two cases with T‐cell lymphoma, myeloproliferative disorder, and marrow eosinophilia with a t(8;12)(p11;q15) and ins(12;8)(p11;p11p21), respectively. For the patient with the t(8;11), the chromosome 11 breakpoint was determined to be in the vicinity of NUP98 . We conclude that 1) all mRNA fusions in EMS result in splicing to FGFR1 exon 9 but breakpoints in FOP are variable, 2) two‐color FISH can identify patients with EMS, and 3) the t(8;17)(p11;q25), t(8;11)(p11;p15), t(8;12)(p11;q15), and ins(12;8)(p11;p11p21) are novel karyotypic changes that most likely involve FGFR1 . © 2001 Wiley‐Liss, Inc.