DNA methylation and copy number variation profiling of T-cell lymphoblastic leukemia and lymphoma
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DNA methylation and copy number variation profiling of T-cell lymphoblastic leukemia and lymphoma. / Haider, Zahra; Landfors, Mattias; Golovleva, Irina; Erlanson, Martin; Schmiegelow, Kjeld; Flægstad, Trond; Kanerva, Jukka; Norén-Nyström, Ulrika; Hultdin, Magnus; Degerman, Sofie.
I: Blood Cancer Journal, Bind 10, 45, 04.2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - DNA methylation and copy number variation profiling of T-cell lymphoblastic leukemia and lymphoma
AU - Haider, Zahra
AU - Landfors, Mattias
AU - Golovleva, Irina
AU - Erlanson, Martin
AU - Schmiegelow, Kjeld
AU - Flægstad, Trond
AU - Kanerva, Jukka
AU - Norén-Nyström, Ulrika
AU - Hultdin, Magnus
AU - Degerman, Sofie
PY - 2020/4
Y1 - 2020/4
N2 - 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.
AB - 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.
U2 - 10.1038/s41408-020-0310-9
DO - 10.1038/s41408-020-0310-9
M3 - Journal article
C2 - 32345961
AN - SCOPUS:85083959026
VL - 10
JO - Blood Cancer Journal
JF - Blood Cancer Journal
SN - 2044-5385
M1 - 45
ER -
ID: 243058297