8p11.2 Translocations: Prevalence, FISH Analysis for FGFR1 and MYST3, and Clinicopathologic Correlates in a Consecutive Cohort of 13 Cases From a Single Institution.

Chromosomal translocations involving 8p11.2 give rise to diverse oncogenic fusion genes including FGFR1 and MYST3. FGFR1 rearrangements have been associated with the stem cell leukemia/lymphoma (SCLL) syndrome, which is a mixed myeloid-lymphoid malignancy characterized by eosinophilia, monocytosis and rapid disease progression into acute myeloid leukemia or lymphoblastic lymphoma. MYST3 is a histone acetyltransferase whose rearrangement has been associated with acute myeloid leukemia (AML; usually monocytic).

The Mayo Clinic cytogenetic database spanning the years 1988–2009 was screened for 8p11.2 translocations. Bone marrow (BM) pathology and cytogenetic results were re-reviewed and relevant clinical information was retrospectively obtained. Archived BM specimens were analyzed by FISH to identify FGFR1 and/or MYST3 rearrangements. BAC clones used for direct-labeled break-apart FISH probes for FGFR1 were CTC-497A2, RP11-90P5 and RP11-513D5 for the 5' portion and RP11-675F6 and RP11-495O10 for the 3' portion; those used for direct-labeled dual color, dual fusion FISH probes for MYST3 were RP11-589C21, CTD-2532C15, RP11-45I11 and RP11-411A18 and for CREBBP (16p13.3) were RP11-737F1, RP11-136I22, Rp11-962J17 and CTD-2514E9.

Out of 24,262 unique patient cytogenetic studies, 8p11.2 translocations were identified in 14 (∼0.06%) patients; 6 constituted sole abnormalities. BM specimens for FISH analysis were available in 13 patients (age range 52–75 years; 8 males). Twelve of these 13 patients had myeloid neoplasms and one had lymphoma; the latter patient had a t(8;10)(p11.2;p13) translocation as a subclone of a 14q32 abnormality and neither FGFR1 nor MYST3 were involved. Among the 12 patients with myeloid neoplasms, FISH analysis revealed abnormalities of MYST3 in 4 patients, FGFR1 in 4 patients, and neither in 4 patients.

The MYST3 abnormalities included MYST3-CREBBP in 2 patients, MYST3-EP300 in one patient and MYST3 amplification in one patient; specific diagnoses included AML with or without antecedent chronic myeloid malignancy. Only one of the 4 patients with FGFR1 rearrangements displayed peripheral blood eosinophilia; specific diagnoses included chronic myeloid malignancy and AML. Three of the remaining 4 patients with neither FGFR1 nor MYST3 abnormalities had highly complex cytogenetic abnormalities except one who had sole t(8;13)(p11.2,q12) and presented with lymphadenopathy (precursor-T cell lymphoblastic lymphoma), marked leukocytosis, eosinophilia, monocytosis, and a BM morphology consistent with MPN (marked myeloproliferation with granulocytosis and eosinophilia). Survival was uniformly poor in all 8p11.2 translocations.

8p11.2 translocations are rarely encountered in routine clinical practice and are usually associated with aggressive myeloid malignancies. In the current unselected series of patients, peripheral blood eosinophilia was not a typical feature of the myeloid neoplasm phenotype associated with FGFR1 translocation. Conversely, at least by FISH, FGFR1 was not involved in an 8p11.2-associated myeloid neoplasm that exhibited SCLL-like features. Additional molecular studies are planned to validate the current findings.

No relevant conflicts of interest to declare.