Karyotypic and ras gene mutational analysis in idiopathic myelofibrosis

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Abstract
Summary. Karyotypic analysis was performed in a total of 69 patients with well-characterized idiopathic myelofibrosis. Karyotypic abnormalities were detected in 46% of cases examined during the chronic phase (29/63); with three abnormalities, del (13q), del(20q) and partial trisomy 1q, accounting for 75% of all abnormalities at diagnosis. The absence of del(5q), trisomy 8 and 21, as well as the rarity of monosomy 7, contrasts with pooled published data and may reflect our exclusion of closely related disorders, in particular MDS with fibrosis. Chromosomal aberrations increased to approximately 90% (8/9) in patients analysed during acute transformation. Mutational activation of codons 12, 13 and 61 of N-, Ha- and Ki-ras genes were assessed by polymerase chain reaction and hydridization with synthetic non-radioactive digoxigenin-labelled probes. Three mutations were detected in samples of peripheral blood DNA taken from 50 patients during the chronic phase of their disease: one N12 Asp (GGT GAT) and two N12 Ser (GGT AGT) mutations. The results from this study indicate that karyotypic abnormalities are present in at least 29% of cases at diagnosis and that del(13q), del(20q) and partial trisomy 1q are the most frequent findings. Ras mutations were relatively infrequent (6%) and appeared restricted to the N-ras gene. Karyotypic analysis at diagnosis was found to be of prognostic significance.