Genomic characterization of pediatric B-lymphoblastic lymphoma and B-lymphoblastic leukemia using formalin-fixed tissues

Julia A. Meyer, Delu Zhou, Clinton C. Mason, Jonathan M. Downie, Vladimir Rodic, Minnie Abromowitch, Birte Wistinghausen, Amanda M. Termuhlen, Anne L. Angiolillo, Sherrie L. Perkins, Mark A. Lones, Phillip Barnette, Joshua D. Schiffman, Rodney R. Miles

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Recurrent genomic changes in B-lymphoblastic leukemia (B-ALL) identified by genome-wide single-nucleotide polymorphism (SNP) microarray analysis provide important prognostic information, but gene copy number analysis of its rare lymphoma counterpart, B-lymphoblastic lymphoma (B-LBL), is limited by the low incidence and lack of fresh tissue for genomic testing. Procedure: We used molecular inversion probe (MIP) technology to analyze and compare copy number alterations (CNAs) in archival formalin-fixed paraffin-embedded pediatric B-LBL (n = 23) and B-ALL (n = 55). Results: Similar to B-ALL, CDKN2A/B deletions were the most common alteration identified in 6/23 (26%) B-LBL cases. Eleven of 23 (48%) B-LBL patients were hyperdiploid, but none showed triple trisomies (chromosomes 4, 10, and 17) characteristic of B-ALL. IKZF1 and PAX5 deletions were observed in 13 and 17% of B-LBL, respectively, which was similar to the reported frequency in B-ALL. Immunoglobulin light chain lambda (IGL) locus deletions consistent with normal light chain rearrangement were observed in 5/23 (22%) B-LBL cases, compared with only 1% in B-ALL samples. None of the B-LBL cases showed abnormal, isolated VPREB1 deletion adjacent to IGL locus, which we identified in 25% of B-ALL. Conclusions: Our study demonstrates that the copy number profile of B-LBL is distinct from B-ALL, suggesting possible differences in pathogenesis between these closely related diseases.

Original languageEnglish (US)
Article numbere26363
JournalPediatric Blood and Cancer
Volume64
Issue number7
DOIs
StatePublished - Jul 2017

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Formaldehyde
Pediatrics
Immunoglobulin lambda-Chains
Molecular Probes
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 4
Polyploidy
Gene Dosage
Trisomy
Microarray Analysis
Paraffin
Single Nucleotide Polymorphism
Lymphoma
Genome
Technology
Light
Incidence

Keywords

  • genomics
  • leukemia
  • lymphoma
  • pediatrics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Genomic characterization of pediatric B-lymphoblastic lymphoma and B-lymphoblastic leukemia using formalin-fixed tissues. / Meyer, Julia A.; Zhou, Delu; Mason, Clinton C.; Downie, Jonathan M.; Rodic, Vladimir; Abromowitch, Minnie; Wistinghausen, Birte; Termuhlen, Amanda M.; Angiolillo, Anne L.; Perkins, Sherrie L.; Lones, Mark A.; Barnette, Phillip; Schiffman, Joshua D.; Miles, Rodney R.

In: Pediatric Blood and Cancer, Vol. 64, No. 7, e26363, 07.2017.

Research output: Contribution to journalArticle

Meyer, JA, Zhou, D, Mason, CC, Downie, JM, Rodic, V, Abromowitch, M, Wistinghausen, B, Termuhlen, AM, Angiolillo, AL, Perkins, SL, Lones, MA, Barnette, P, Schiffman, JD & Miles, RR 2017, 'Genomic characterization of pediatric B-lymphoblastic lymphoma and B-lymphoblastic leukemia using formalin-fixed tissues', Pediatric Blood and Cancer, vol. 64, no. 7, e26363. https://doi.org/10.1002/pbc.26363
Meyer, Julia A. ; Zhou, Delu ; Mason, Clinton C. ; Downie, Jonathan M. ; Rodic, Vladimir ; Abromowitch, Minnie ; Wistinghausen, Birte ; Termuhlen, Amanda M. ; Angiolillo, Anne L. ; Perkins, Sherrie L. ; Lones, Mark A. ; Barnette, Phillip ; Schiffman, Joshua D. ; Miles, Rodney R. / Genomic characterization of pediatric B-lymphoblastic lymphoma and B-lymphoblastic leukemia using formalin-fixed tissues. In: Pediatric Blood and Cancer. 2017 ; Vol. 64, No. 7.
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abstract = "Background: Recurrent genomic changes in B-lymphoblastic leukemia (B-ALL) identified by genome-wide single-nucleotide polymorphism (SNP) microarray analysis provide important prognostic information, but gene copy number analysis of its rare lymphoma counterpart, B-lymphoblastic lymphoma (B-LBL), is limited by the low incidence and lack of fresh tissue for genomic testing. Procedure: We used molecular inversion probe (MIP) technology to analyze and compare copy number alterations (CNAs) in archival formalin-fixed paraffin-embedded pediatric B-LBL (n = 23) and B-ALL (n = 55). Results: Similar to B-ALL, CDKN2A/B deletions were the most common alteration identified in 6/23 (26{\%}) B-LBL cases. Eleven of 23 (48{\%}) B-LBL patients were hyperdiploid, but none showed triple trisomies (chromosomes 4, 10, and 17) characteristic of B-ALL. IKZF1 and PAX5 deletions were observed in 13 and 17{\%} of B-LBL, respectively, which was similar to the reported frequency in B-ALL. Immunoglobulin light chain lambda (IGL) locus deletions consistent with normal light chain rearrangement were observed in 5/23 (22{\%}) B-LBL cases, compared with only 1{\%} in B-ALL samples. None of the B-LBL cases showed abnormal, isolated VPREB1 deletion adjacent to IGL locus, which we identified in 25{\%} of B-ALL. Conclusions: Our study demonstrates that the copy number profile of B-LBL is distinct from B-ALL, suggesting possible differences in pathogenesis between these closely related diseases.",
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T1 - Genomic characterization of pediatric B-lymphoblastic lymphoma and B-lymphoblastic leukemia using formalin-fixed tissues

AU - Meyer, Julia A.

AU - Zhou, Delu

AU - Mason, Clinton C.

AU - Downie, Jonathan M.

AU - Rodic, Vladimir

AU - Abromowitch, Minnie

AU - Wistinghausen, Birte

AU - Termuhlen, Amanda M.

AU - Angiolillo, Anne L.

AU - Perkins, Sherrie L.

AU - Lones, Mark A.

AU - Barnette, Phillip

AU - Schiffman, Joshua D.

AU - Miles, Rodney R.

PY - 2017/7

Y1 - 2017/7

N2 - Background: Recurrent genomic changes in B-lymphoblastic leukemia (B-ALL) identified by genome-wide single-nucleotide polymorphism (SNP) microarray analysis provide important prognostic information, but gene copy number analysis of its rare lymphoma counterpart, B-lymphoblastic lymphoma (B-LBL), is limited by the low incidence and lack of fresh tissue for genomic testing. Procedure: We used molecular inversion probe (MIP) technology to analyze and compare copy number alterations (CNAs) in archival formalin-fixed paraffin-embedded pediatric B-LBL (n = 23) and B-ALL (n = 55). Results: Similar to B-ALL, CDKN2A/B deletions were the most common alteration identified in 6/23 (26%) B-LBL cases. Eleven of 23 (48%) B-LBL patients were hyperdiploid, but none showed triple trisomies (chromosomes 4, 10, and 17) characteristic of B-ALL. IKZF1 and PAX5 deletions were observed in 13 and 17% of B-LBL, respectively, which was similar to the reported frequency in B-ALL. Immunoglobulin light chain lambda (IGL) locus deletions consistent with normal light chain rearrangement were observed in 5/23 (22%) B-LBL cases, compared with only 1% in B-ALL samples. None of the B-LBL cases showed abnormal, isolated VPREB1 deletion adjacent to IGL locus, which we identified in 25% of B-ALL. Conclusions: Our study demonstrates that the copy number profile of B-LBL is distinct from B-ALL, suggesting possible differences in pathogenesis between these closely related diseases.

AB - Background: Recurrent genomic changes in B-lymphoblastic leukemia (B-ALL) identified by genome-wide single-nucleotide polymorphism (SNP) microarray analysis provide important prognostic information, but gene copy number analysis of its rare lymphoma counterpart, B-lymphoblastic lymphoma (B-LBL), is limited by the low incidence and lack of fresh tissue for genomic testing. Procedure: We used molecular inversion probe (MIP) technology to analyze and compare copy number alterations (CNAs) in archival formalin-fixed paraffin-embedded pediatric B-LBL (n = 23) and B-ALL (n = 55). Results: Similar to B-ALL, CDKN2A/B deletions were the most common alteration identified in 6/23 (26%) B-LBL cases. Eleven of 23 (48%) B-LBL patients were hyperdiploid, but none showed triple trisomies (chromosomes 4, 10, and 17) characteristic of B-ALL. IKZF1 and PAX5 deletions were observed in 13 and 17% of B-LBL, respectively, which was similar to the reported frequency in B-ALL. Immunoglobulin light chain lambda (IGL) locus deletions consistent with normal light chain rearrangement were observed in 5/23 (22%) B-LBL cases, compared with only 1% in B-ALL samples. None of the B-LBL cases showed abnormal, isolated VPREB1 deletion adjacent to IGL locus, which we identified in 25% of B-ALL. Conclusions: Our study demonstrates that the copy number profile of B-LBL is distinct from B-ALL, suggesting possible differences in pathogenesis between these closely related diseases.

KW - genomics

KW - leukemia

KW - lymphoma

KW - pediatrics

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U2 - 10.1002/pbc.26363

DO - 10.1002/pbc.26363

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