Acute lymphoblastic leukemia with low hypodiploid/near triploid karyotype is a specific clinical entity and exhibits a very high TP53 mutation frequency of 93%. Issue 6 (11th March 2014)

• Record Type: Journal Article
• Authors: Mühlbacher, Verena; Zenger, Melanie; Schnittger, Susanne; Weissmann, Sandra; Kunze, Franziska; Kohlmann, Alexander; Bellos, Frauke; Kern, Wolfgang; Haferlach, Torsten; Haferlach, Claudia
• Is Part Of: Genes, chromosomes & cancer. Volume 53:Issue 6(2014:Jun.)
• Page Start: 524
• Page End: 536
• Publication Date: 2014-03-11
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22163
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>B lymphoblastic leukemia/lymphoma (ALL) are subdivided by the WHO classification into five subgroups defined by specific translocations and two further subgroups defined by the number of chromosomes. The hypodiploid subgroup is heterogeneous and comprises ALL with a chromosome number of <46. To characterize a specific subset with low hypodiploid karyotype, we performed chromosome banding analysis, FISH, array comparative genomic hybridization, and mutational analyses of <italic>FBXW7</italic>, <italic>NOTCH1</italic>, <italic>KRAS</italic>, <italic>NRAS</italic>, <italic>TP53</italic>, and <italic>IKZF1</italic> in 29 cases. We observed a nonrandom pattern of chromosome losses, including chromosomes 3, 7, 13, 15, 16, and 17. A deletion encompassing the <italic>CDKN2A/B</italic> locus was the only recurrent structural abnormality. A duplication of the low hypodiploid karyotype occurred frequently, resulting in a near triploid karyotype based on the definition by merely counting chromosomes but in fact was a very low tetraploid chromosome set. Mutational analyses revealed no mutations in <italic>IKZF1</italic>, <italic>FBXW7, NOTCH1</italic>, and <italic>KRAS</italic> and only one mutation in <italic>NRAS</italic>. However, we discovered a high frequency of <italic>TP53</italic> mutations in 93% (27/29) of cases. In 26/27 cases with <italic>TP53</italic> mutation, the second <italic>TP53</italic> allele was lost due to monosomy 17. Median overall survival was short (18.5 months), which might be related to the high frequency of <italic>TP53</italic> alterations. Therefore, ALL with low hypodiploidy is characterized by a typical pattern of chromosome losses and a remarkably high <italic>TP53</italic> mutation frequency. Our data suggest the introduction of a novel WHO entity within the B lymphoblastic leukemia/lymphoma group showing low hypodiploid/very low tetraploid karyotype and concomitant <italic>TP53</italic> mutation. © 2014 Wiley Periodicals, Inc.</p> </abstract>