The JAK2 gene is located on chromosome 9p24.1, its product is a tyrosine kinase protein that plays a role in signal transduction between membrane receptors for growth factors and intracellular signaling molecules and is also involved in cytokine signaling. Mutation V617F of JAK2 (Janus kinase 2) causes violation of autoinhibiting activity and promotes malignant transformation and proliferation. Recent studies, however, indicate a possible amplification of somatic chromosome 9p24.1 region encoding the JAK2 in triple-negative breast cancer (TNBC) in connection with a poorer prognosis and shorter survival.
The aim of our pilot study was to perform a cytogenetic and molecular biological analysis of the JAK2 gene in a cohort of 40 patients diagnosed and confirmed with TNBC. The FISH method was used to analyze numerical changes and translocations, including the detection of possible merger partners. In the next step mutation analysis was by PCR and direct sequencing performed.
On the basis of cytogenetic and molecular changes of the JAK2 gene, it can be stated that the numerical, structural and molecular changes occur in TNBC at a high frequency. In addition to amplification which is a potential predictor of ruxolotinib inhibition, a number of numerical and structural changes (including point mutations) of the gene was detected (amplification detected in 25% of cases, polysomy detected in 15% of cases, monosomy detected in 5% of cases, break detection in 10% of cases, amplification/break detected in 10% of cases). Mutational analysis showed the presence of the V617F mutation in 15% of cases where there was normal cytogenetics.
These changes may potentially cause worse response to treatment with an inhibitor and will require us to focus attention in this direction.
Clinical trial identification
Legal entity responsible for the study
First Faculty of Medicine.
This work was supported by the Charles University research program PROGRESQ 28 (Oncology).
This work was supported by the Charles University research program PROGRES Q 28 (Oncology)
All authors have declared no conflicts of interest.