Abstract
The acquired mutation Val617Phe in the tyrosine kinase JAK2 was recently identified in most but not all patients with classical myeloproliferative disorders. We describe a cytogenetic and molecular study of a JAK2Val617Phe-negative case of essential thrombocythemia harboring the acquired translocation t(X;5)(q13;q33). We show that this involves the inactive X-chromosome and is associated with silencing of autosomal genes within the adjacent 5q minus syndrome common deleted region. This is the first documented example of autosomal gene silencing adjacent to an X-autosome breakpoint in human malignancy and such a mechanism may underlie the pathogenesis of related disorders with translocations involving Xq13.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Substitution
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Base Sequence
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Blotting, Southern
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Bone Marrow / pathology
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Breast Neoplasms / complications
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Breast Neoplasms / genetics
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Chromosome Disorders / complications
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Chromosome Disorders / genetics*
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Chromosome Mapping
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Chromosome Walking / methods
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Chromosomes, Human, Pair 5*
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Chromosomes, Human, X*
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DNA Methylation
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DNA Primers
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Female
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Humans
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Janus Kinase 2
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Middle Aged
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Phenylalanine
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Protein-Tyrosine Kinases / genetics*
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Proto-Oncogene Proteins / genetics*
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Reverse Transcriptase Polymerase Chain Reaction
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Sex Chromosome Disorders / complications
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Sex Chromosome Disorders / genetics*
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Thrombocythemia, Essential / complications
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Thrombocythemia, Essential / genetics*
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Thrombocythemia, Essential / pathology
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Translocation, Genetic*
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Valine
Substances
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DNA Primers
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Proto-Oncogene Proteins
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Phenylalanine
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Protein-Tyrosine Kinases
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JAK2 protein, human
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Janus Kinase 2
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Valine