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DNA methylation and copy number variation profiling of T-cell lymphoblastic leukemia and lymphoma

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  • Zahra Haider
  • Mattias Landfors
  • Irina Golovleva
  • Martin Erlanson
  • Kjeld Schmiegelow
  • Trond Flægstad
  • Jukka Kanerva
  • Ulrika Norén-Nyström
  • Magnus Hultdin
  • Sofie Degerman
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Despite having common overlapping immunophenotypic and morphological features, T-cell lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) have distinct clinical manifestations, which may represent separate diseases. We investigated and compared the epigenetic and genetic landscape of adult and pediatric T-ALL (n = 77) and T-LBL (n = 15) patient samples by high-resolution genome-wide DNA methylation and Copy Number Variation (CNV) BeadChip arrays. DNA methylation profiling identified the presence of CpG island methylator phenotype (CIMP) subgroups within both pediatric and adult T-LBL and T-ALL. An epigenetic signature of 128 differentially methylated CpG sites was identified, that clustered T-LBL and T-ALL separately. The most significant differentially methylated gene loci included the SGCE/PEG10 shared promoter region, previously implicated in lymphoid malignancies. CNV analysis confirmed overlapping recurrent aberrations between T-ALL and T-LBL, including 9p21.3 (CDKN2A/CDKN2B) deletions. A significantly higher frequency of chromosome 13q14.2 deletions was identified in T-LBL samples (36% in T-LBL vs. 0% in T-ALL). This deletion, encompassing the RB1, MIR15A and MIR16-1 gene loci, has been reported as a recurrent deletion in B-cell malignancies. Our study reveals epigenetic and genetic markers that can distinguish between T-LBL and T-ALL, and deepen the understanding of the biology underlying the diverse disease localization.

Original languageEnglish
JournalBlood Cancer Journal
Volume10
Issue number4
Pages (from-to)45
ISSN2044-5385
DOIs
Publication statusPublished - 28 Apr 2020

    Research areas

  • Adolescent, Adult, Aged, Biomarkers, Tumor/genetics, Child, Child, Preschool, CpG Islands, DNA Copy Number Variations, DNA Methylation, Gene Expression Profiling/methods, Humans, Infant, Middle Aged, Phenotype, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/classification, Prognosis, Young Adult

ID: 62071486