Inactivation of p53 and amplification of MYCN

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• 作者：Katerina Stano-Kozubik ; Jitka Malcikova ; Boris Tichy ; Jana Kotaskova ; Marek Borsky ; Viera Hrabcakova ; Hana Francova ; Iveta Valaskova ; Ludmila Bourkova ; Jana Smardova ; Michael Doubek ; Yvona Brychtova
• 刊名：Cancer Genetics and Cytogenetics
• 出版年：2009
• 出版时间：February 2009
• 年：2009
• 卷：189
• 期：1
• 页码：53-58
• 全文大小：295 K

文摘

B-cell chronic lymphocytic leukemia (CLL) is an incurable disease with a highly variable clinical course. A proportion of patients eventually progress to a higher stage of malignancy. A recent association has been observed between the presence of aberrant somatic hypermutations in leukemic cells (hypermutations occurring outside of the immunoglobulin locus) and the transformation to a diffuse large B-cell lymphoma or prolymphocytic leukemia. In this study, we report on the rarely observed blastic transformation in a CLL patient who had previously been shown to harbor aberrant somatic hypermutations in the TP53 tumor-suppressor gene (Mol Immunol 2008;45:1525–29). The enzyme responsible, the activation-induced cytidine deaminase, was still active within the transformation, as evidenced by the ongoing class-switch recombination of cytoplasmic immunoglobulins. The transformation was accompanied by a complete p53 inactivation, as well as complex karyotype changes including prominent amplification of MYCN oncogene. Our case-study supports the view that the aberrant somatic hypermutation is associated with transformation of CLL to a more aggressive malignancy.