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Genetic and epigenetic characterization of hypodiploid acute lymphoblastic leukemia
Lund University, Sweden.
Lund University, Sweden; University of and Regional Labs, Sweden.
Lund University, Sweden.
Lund University, Sweden.
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2015 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 40, 42793-42802 p.Article in journal (Refereed) Published
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Abstract [en]

Purpose: To investigate the genetic and epigenetic landscape of hypodiploid (<45 chromosomes) acute lymphoblastic leukemia (ALL). Methods: Single nucleotide polymorphism array, whole exome sequencing, RNA sequencing, and methylation array analyses were performed on eleven hypodiploid ALL cases. Results: In line with previous studies, mutations in IKZF3 and FLT3 were detected in near-haploid (25-30 chromosomes) cases. Low hypodiploidy (31-39 chromosomes) was associated with somatic TP53 mutations. Notably, mutations of this gene were also found in 3/3 high hypodiploid (40-44 chromosomes) cases, suggesting that the mutational patterns are similar in low hypodiploid and high hypodiploid ALL. The high hypodiploid ALLs frequently displayed substantial cell-to-cell variability in chromosomal content, indicative of chromosomal instability; a rare phenomenon in ALL. Gene expression analysis showed that genes on heterodisomic chromosomes were more highly expressed in hypodiploid cases. Cases clustered according to hypodiploid subtype in the unsupervised methylation analyses, but there was no association between chromosomal copy number and methylation levels. A comparison between samples obtained at diagnosis and relapse showed that the relapse did not arise from the major diagnostic clone in 3/4 cases. Conclusion: Taken together, our data support the conclusion that near-haploid and low hypodiploid ALL are different with regard to mutational profiles and also suggest that ALL cases with high hypodiploidy may harbor chromosomal instability.

Place, publisher, year, edition, pages
IMPACT JOURNALS LLC , 2015. Vol. 6, no 40, 42793-42802 p.
Keyword [en]
acute lymphoblastic leukemia; hypodiploidy; next generation sequencing; chromosomal instability
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-125836DOI: 10.18632/oncotarget.6000ISI: 000369907900032PubMedID: 26544893OAI: oai:DiVA.org:liu-125836DiVA: diva2:910190
Note

Funding Agencies|Swedish Cancer Society; Swedish Childhood Cancer Foundation; Ellen Bachrachs foundation; Swedish Research Council

Available from: 2016-03-08 Created: 2016-03-04 Last updated: 2017-11-30

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Behrendtz, Mikael
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Faculty of Medicine and Health SciencesDivision of Clinical SciencesDepartment of Paediatrics in Linköping
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