ALLELE BURDEN OF JAK2V617F MUTATION IN PLASMA CELL FREE DNA OF HEALTHY INDIVIDUALS SMOKERS AND NON-SMOKERS

CARDOZO MA,; BOSQUIAZZO VL,; RIERA L, ; FOLLONIER AM,; , ; GAYDOU L, ; RAMOS JG

Congreso; LXISociedad Argentina de Investigación Clínica (SAIC); 2016

Smoking is one of the most studied risk factors associated with the development of cancer and heart disease. Several authors have shown that components of cigarette smoke promote the development of a variety of mutations affecting different genes among which is the V617F mutation in the JAK2 gene.JAK2 is a member of the family of tyrosine kinases that are linked to cytokine receptors constitutively. Its activation stimulates the proliferation, differentiation, migration and cell apoptosis. The V617F mutation corresponds to an autoinhibitory domain, resulting in constitutive activation of the signaling pathway and is one of the major diagnostic criteria of Chronic BCR-ABL negative Myeloproliferative Neoplasms.Since this mutation may be present in healthy individuals; that smoking is a risk factor for its appearance; and that the cell free DNA (cfDNA) sample is representative of various body compartments, then the mutation detection could be a prognostic marker for the development of clonal pathology. Therefore we hypothesized that the allelic burden of JAK2 mutated gene in cfDNA of healthy smokers is significantly higher than in non-smokers.For this purpose samples were collected from healthy individuals: 16 smokers and 14 non-smokers. cfDNA was obtained from plasma using the QIAmp DNA Blood Mini kit. The determination of the allele burden of JAK2V617F (% alleles JAK2V617F/total alleles JAK2) in cfDNA was determined by an allele specific real time PCR assay (qPCR). In order to discard subclinic haematological diseases a blood count for each individual was performed.The JAK2V617F mutation was detected both the cfDNA of smokers and non-smokers. The allele burden in smokers was 0.030% [95% CI:0.017-0.055%], while in non-smokers was 0.111% [95% CI:0.061-0.203%] with statistical significance (p=0.003).These results demonstrate that the mutation could be present either in healthy smokers and non-smokers, and it prognostic value as a tumoral marker must to be investigated.