Chromosome 9p24 abnormalities: prevalence, description of novel JAK2 translocations, JAK2V617F mutation analysis and clinicopathologic correlates

Abstract

Current information is insufficient regarding the prevalence, cytogenetic details, JAK2 involvement, JAK2V617F mutational status, and clinicopathologic correlates of chromosome 9p24 abnormalities. The current study was designed to provide additional data in this regard. The Mayo Clinic cytogenetics database spanning the years 1989-2008 was screened for chromosome 9p24 abnormalities. Bone marrow (BM) morphology was re-reviewed and relevant clinical information retrospectively obtained. Structural abnormalities of JAK2 were examined by FISH and JAK2V617F mutation analysis. Among 24 262 unique patient cytogenetic studies, chromosome 9p24 abnormalities were identified in 25 patients ( approximately 0.06%): 12 with myeloid and 13 with lymphoid neoplasms. The associated karyotype was complex in 12 of the 13 lymphoid but in only four of the 12 myeloid cases. Archived BM was available in 23 cases that allowed additional FISH studies and JAK2V617F mutation analysis. FISH analysis disclosed JAK2 involvement in 10 patients including five myeloid and five lymphoid cases; the associated karyotype was complex in all the lymphoid but in none of the myeloid cases. Five patients displayed previously undescribed JAK2 translocations: t(8;9)(q22;p24), t(9;17)(p24;q23), t(4;9)(q25;p24), t(2;9)(p21;p24) and t(8;9)(q13;p24). JAK2-associated chromosomal translocations, in a non-complex karyotype setting, were documented in four patients, all of whom carried a diagnosis of myeloproliferative neoplasms (MPN) and harbored JAK2V617F. Two patients with diffuse large B cell lymphoma displayed complex karyotype and JAK2 amplification by FISH. Chromosome 9p24 abnormalities are rare and do not always involve JAK2. The subset with JAK2 translocations are usually associated with MPN and harbor JAK2V617F, suggesting a cause-effect relationship. The current study also describes five novel translocations involving JAK2.