Somatic ATM mutations indicate a pathogenic role of ATM in B-cell chronic lymphocytic leukemia

• Verfasst von: Schaffner, Claudia [VerfasserIn]
• Verfasst von: Stilgenbauer, Stephan [VerfasserIn]
• Verfasst von: Rappold, Gudrun [VerfasserIn]
• Verfasst von: Döhner, Hartmut [VerfasserIn]
• Verfasst von: Lichter, Peter [VerfasserIn]
• Titel: Somatic ATM mutations indicate a pathogenic role of ATM in B-cell chronic lymphocytic leukemia
• Verf.angabe: Claudia Schaffner, Stephan Stilgenbauer, Gudrun A. Rappold, Hartmut Döhner, and Peter Lichter
• Jahr: 1999
• Umfang: 6 S.
• Teil: volume:94
• Teil: year:1999
• Teil: number:2
• Teil: pages:748-753
• Teil: extent:6
• Fussnoten: Online 14 December 2020 ; Elektronische Reproduktion der Druck-Ausgabe ; Gesehen am 07.04.2021
• Titel Quelle: Enthalten in: Blood
• Ort Quelle: Washington, DC : American Society of Hematology, 1946
• Jahr Quelle: 1999
• Band/Heft Quelle: 94(1999), 2, Seite 748-753
• ISSN Quelle: 1528-0020
• DOI: doi:10.1182/blood.V94.2.748
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1753223407

Abstract

Deletion in chromosome bands 11q22-q23 is one of the most common chromosome aberrations in B-cell chronic lymphocytic leukemia (B-CLL). It is associated with extensive lymph node involvement and poor survival. The minimal consensus deletion comprises a segment, which contains the ATM gene presenting an interesting candidate gene, as mutations in ATM predispose A-T patients to lymphoid malignancies. To investigate a potential pathogenic role of ATM in B-cell tumorigenesis, we performed mutation analysis of ATM in 29 malignant lymphomas of B-cell origin (B-CLL = 27; mantle cell lymphoma, [MCL] = 2). Twenty-three of these carried an 11q22-q23 deletion. In five B-CLLs and one MCL with deletion of one ATMallele, a point mutation in the remaining allele was detected, which resulted in aberrant transcript splicing, alteration, or truncation of the protein. In addition, mutation analysis identified point mutations in three cases without 11q deletion: two B-CLLs with one altered allele and one MCL with both alleles mutated. In four cases analyzed, theATM alterations were not present in the germ line indicating a somatic origin of the mutations. Our study demonstrates somatic disruption of both alleles of the ATM gene by deletion or point mutation and thus its pathogenic role in sporadic B-cell lineage tumors.