title: A novel TRB@/NOTCH1 fusion gene in T-cell lymphoblastic lymphoma with t(7;9)(q34;q34).
abstract: BACKGROUND
  In T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), activating mutations of NOTCH1 are observed in more than 50% of cases, whereas the t(7;9)(q34;q34) involving NOTCH1 at 9q34 and TRB@ at 7q34 is an extremely rare but recurrent translocation.
  
  
  METHODS
  A 41-year-old male with a large mediastinal mass, pleural effusion, and lymphadenopathy was diagnosed as having T-LBL. Lymphoma cells were positive for CD4, CD8, CD2, CD3, CD5, CD7, CD10, and TdT.
  
  
  RESULTS
  G-banding and spectral karyotyping of pleural effusion cells showed 47,XY,dup(1)(q21q32),t(7;9)(q34;q34),+20. Genomic polymerase chain reaction (PCR) revealed that the 5' end of TRB@ J1-5 was connected with the middle of NOTCH1 exon 25 (434 bp downstream from its 5' end) in a 'head-to-head' configuration on the der(9)t(7;9), although nine extra bases were inserted between the two genes. Reverse transcription-PCR confirmed expression of the TRB@/NOTCH1 fusion transcripts. Similarly, the 5' end of J1-5 was fused to the shortened exon 25 with nine extra bases. The NOTCH1 breakpoint in exon 25 was very close to transcription start sites of deleted Notch1 in murine T-ALL.
  
  
  CONCLUSIONS
  The TRB@/NOTCH1 fusion gene with a NOTCH1 breakpoint in exon 25, which has not previously been detected in four other reported cases with t(7;9), could lead to aberrant expression of the truncated NOTCH1 by TRB@ enhancer elements. The resultant NOTCH1 receptor deleting most of the extracellular domain may be implicated in the pathogenesis of T-LBL by ligand-independent, constitutive activation of the NOTCH1 pathway, suggesting avenues for future therapy with γ-secretase inhibitors.
authors.affiliation: Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. kyamamo@med.kobe-u.ac.jp
authors.forename: Katsuya
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamachi
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Yakushijin
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Miyata
authors.forename: Atsuo
authors.initials: A
authors.lastname: Okamura
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
mesh_terms: D000328:Adult; D001483:Base Sequence; D002871:Chromosome Banding; D056905:Chromosome Breakpoints; D002897:Chromosomes, Human, Pair 7; D002899:Chromosomes, Human, Pair 9; D023061:Gene Order; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D050596:Oncogene Fusion; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics*; D051881:Receptor, Notch1 / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016415:Sequence Alignment; D014178:Translocation, Genetic
chemical_list: D015514:Oncogene Proteins, Fusion; D051881:Receptor, Notch1; D016693:Receptors, Antigen, T-Cell, alpha-beta