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Warnstorf, Daria; Bawadi, Randa; Schienke, Andrea; Strasser, Renate; Schmidt, Gunnar; Illig, Thomas; Tauscher, Marcel; Thol, Felicitas; Heuser, Michael; Steinemann, Doris; Davenport, Claudia; Schlegelberger, Brigitte; Behrens, Yvonne Lisa; Göhring, Gudrun

Unbalanced translocation der(5;17) resulting in a TP53 loss as recurrent aberration in myelodysplastic syndrome and acute myeloid leukemia with complex karyotype

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  • Media type: E-Article
  • Title: Unbalanced translocation der(5;17) resulting in a TP53 loss as recurrent aberration in myelodysplastic syndrome and acute myeloid leukemia with complex karyotype
  • Contributor: Warnstorf, Daria; Bawadi, Randa; Schienke, Andrea; Strasser, Renate; Schmidt, Gunnar; Illig, Thomas; Tauscher, Marcel; Thol, Felicitas; Heuser, Michael; Steinemann, Doris; Davenport, Claudia; Schlegelberger, Brigitte; Behrens, Yvonne Lisa; Göhring, Gudrun
  • imprint: Wiley, 2021
  • Published in: Genes, Chromosomes and Cancer
  • Language: English
  • DOI: 10.1002/gcc.22938
  • ISSN: 1045-2257; 1098-2264
  • Keywords: Cancer Research ; Genetics
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>A complex karyotype, detected in myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML), is associated with a reduced median survival. The most frequent chromosomal aberrations in complex karyotypes are deletions of 5q and 17p harboring the tumor suppressor gene <jats:italic>TP53</jats:italic>. The unbalanced translocation der(5;17) involving chromosome 5q and 17p is a recurrent aberration in MDS/AML, resulting in <jats:italic>TP53</jats:italic> loss. We analyzed the karyotypes of 178 patients with an unbalanced translocation der(5;17) using fluorescence R−/G‐banding analysis. Whenever possible, fluorescence in situ hybridization (FISH) (n = 138/141), multicolor FISH (n = 8), telomere length measurement (n = 9), targeted DNA sequencing (n = 13), array‐CGH (n = 7) and targeted RNA sequencing (n = 2) were conducted. The der(5;17) aberration was accompanied with loss of genetic material in 7q (53%), −7 (27%), gain of 21q (29%), +8 (17%) and − 18 (16%) and all analyzed patients (n = 13) showed a (likely) pathogenic variant in<jats:italic>TP53</jats:italic>. The der(5;17) cohort showed significantly shortened telomeres in comparison to the healthy age‐matched controls (<jats:italic>P</jats:italic> &lt; .05), but there was no significant telomere shortening in comparison to MDS/AML patients with a complex karyotype without der(5;17). No fusion genes resulted from the unbalanced translocation. This study demonstrates that the unbalanced translocation der(5;17) is associated with a biallelic inactivation of <jats:italic>TP53</jats:italic> due to a deletion of <jats:italic>TP53</jats:italic> in one allele and a pathogenic variant of the second <jats:italic>TP53</jats:italic> allele. Since the breakpoints are located within (near‐) heterochromatic regions, alterations of DNA methylation or histone modifications may be involved in the generation of der(5;17).</jats:p>