title: Genomic characterization of pediatric B-lymphoblastic lymphoma and B-lymphoblastic leukemia using formalin-fixed tissues.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Oncological Sciences, University of Utah, Salt Lake City, Utah.|Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Meyer
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, Utah.
authors.forename: Delu
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Clinton C
authors.initials: CC
authors.lastname: Mason
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, Utah.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Downie
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, Utah.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Rodic
authors.affiliation: Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Minnie
authors.initials: M
authors.lastname: Abromowitch
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Birte
authors.initials: B
authors.lastname: Wistinghausen
authors.affiliation: Department of Pediatrics, Keck School of Medicine at the University of Southern California, Children's Hospital Los Angeles, Los Angeles, California.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Termuhlen
authors.affiliation: Division of Oncology, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, District of Columbia.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Angiolillo
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, Utah.|ARUP Institute for Experimental Pathology, Salt Lake City, Utah.
authors.forename: Sherrie L
authors.initials: SL
authors.lastname: Perkins
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lones
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Phillip
authors.initials: P
authors.lastname: Barnette
authors.affiliation: Department of Oncological Sciences, University of Utah, Salt Lake City, Utah.|Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.|Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Schiffman
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.|Department of Pathology, University of Utah, Salt Lake City, Utah.|ARUP Institute for Experimental Pathology, Salt Lake City, Utah.
authors.forename: Rodney R
authors.initials: RR
authors.lastname: Miles
mesh_terms: D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D005260:Female; D005557:Formaldehyde; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics; D008297:Male; D016612:Paraffin Embedding; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D016707:Tissue Fixation
chemical_list: D005557:Formaldehyde
keywords: genomics; leukemia; lymphoma; pediatrics