Abstract
Detection of JAK2 V617F mutation is quickly becoming a front-line screening test for suspected myeloproliferative disorders (MPDs), as the mutation shows high frequency and specificity in non-CML MPDs, PV, ET or CIMF. Routine cytogenetics can detect chromosome abnormalities in approximately 20% of MPDs and is very helpful in establishing or confirming the presence of aberrant clonality, although chromosome changes are often numerical gains and losses, deemed non-specific. To see if there is correlation between JAK2 mutation and karyotypes, we studied 57 consecutive patients with clinically and morphologically confirmed diagnosis of non-CML MPDs. JAK2 V617F mutation performed using allele-specific PCR (sensitive to 10% using pyrosequencing) was found in 72% of patients (41/57), whereas clonal chromosome abnormalities were observed in 15.8% (9/57). There was no correlation between JAK2 mutational status and karyotypes. In 41 patients positive for the JAK2 mutation, 6 were cytogenetically abnormal and 35 normal. In 16 patients negative for the mutation, 3 showed abnormal karyotypes and 13 had normal karyotypes (X2 test, p>0.5). Among 6 patients with both JAK2 mutation and an abnormal karyotype, JAK2 mutation was seen in >50% of each sample in 4 patients, consistent with a homozygous mutation. Interestingly, in two cases, one with PV and trisomy 9 and another with MPD unclassifiable and trisomy 9p resulting from an unbalanced translocation between chromosomes 9p and 13, JAK2 mutation was present in >65% of each sample. Trisomy 9 and trisomy 9p are common abnormalities in MPDs, particularly in PV, seen in over 20% of cytogenetically abnormal cases. JAK2 gene is located on 9p24. Mitotic recombination is considered the most likely cause of loss of heterozygosity (LOH) and thus mutant homozygosity which is undetectable at the cytogenetic level. However, in cases with trisomy 9 or 9p, the JAK2 allele genotypes may be G/T/T and/or T/T/T as well as the usual G/T and/or T/T. Our observations suggest that trisomy 9 or 9p should be taken into consideration when interpreting JAK2 mutation status and that further molecular studies are needed to delineate the implication of trisomy 9 or 9p in potential mutant allele selective advantage and clonal evolution in JAK2 mutation positive MPDs.
Trisomy 9p
