The JAK2 V617F somatic mutation is present in the majority of patients with myeloproliferative cancer (polycythaemia vera, essential thrombocytosis, and primary myelofibrosis). However, the diagnostic value of the JAK2 V617F somatic mutation for myeloproliferative cancer in the general population is unknown. We examined this question in 49 488 individuals from the Copenhagen General Population Study. We also examined the association between JAK2 V617F somatic mutation, rs10974944 germline genotype, haematological phenotype, any cancer, haematological cancer, myeloproliferative cancer, ischaemic heart disease, and venous thromboembolism. The JAK2 V617F somatic mutation was present in 0·1% (n = 68), increasing across rs10974944 germline genotypes (P-trend = 0·001). JAK2 V617F somatic mutation positives versus negatives had higher erythrocyte (P = 2 × 10(-5) ), thrombocyte (P = 2 × 10(-16) ), and leucocyte (P = 4 × 10(-9) ) counts, and had 2·7-/2·5-fold risk of cancer (prevalent/incident), 44-/28-fold risk of haematological cancer, 221-/97-fold risk of myeloproliferative cancer, 2·2-/1·2-fold risk of ischaemic heart disease, and 3·1-/1·0-fold risk of venous thromboembolism. By combining conventional haematological parameters with a test for the JAK2 V617F somatic mutation, myelo;?>proliferative cancer could be identified or ruled out with a sensitivity of 47-100% and a specificity of 98-100%. In conclusion, in the general population the JAK2 V617F somatic mutation has a high diagnostic value for myeloproliferative cancer when combined with conventional haematological parameters.
British Journal of Haematology, 2013, Vol 160, Issue 1, p. 70-9