8p11.2 Translocations: Prevalence, FISH Analysis for FGFR1 and MYST3, and Clinicopathologic Correlates in a Consecutive Cohort of 13 Cases From a Single Institution.
Authors: Patnaik Mrinal M , Knudson Ryan A , Hanson Curtis A. , Ketterling Rhett P , Tefferi Ayalew 
Published: October 2019

Abstract
Abstract 1887
Poster Board I-910

Background:
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).

Methods:
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.

Results:
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.

Conclusions:
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.

Disclosures:
No relevant conflicts of interest to declare.