title: Characterization of clonal immunoglobulin heavy (IGH) V-D-J gene rearrangements and the complementarity-determining region in South Indian patients with precursor B-cell acute lymphoblastic leukemia.
abstract: BACKGROUND
  This study characterized clonal IG heavy V-D-J (IGH) gene rearrangements in South Indian patients with precursor B-cell acute lymphoblastic leukemia (precursor B-ALL) and identified age-related predominance in VDJ rearrangements.
  
  
  METHODS
  IGH rearrangements were studied in 50 precursor B-ALL cases (common ALL=37, pre-B ALL=10, pro-B ALL=3) by polymerase chain reaction (PCR) heteroduplex analysis. Twenty randomly selected clonal IGH rearrangement sequences were analyzed using the IMGT/V-QUEST tool.
  
  
  RESULTS
  Clonal IGH rearrangements were detected in 41 (82%) precursor B-ALL cases. Among the IGHV1-IGHV7 subgroups, IGHV3 was used in 25 (50%) cases. Among the IGHD1-IGHD7 genes, IGHD2 and IGHD3 were used in 8 (40%) and 5 (25%) clones, respectively. Among the IGHJ1-IGHJ6 genes, IGHJ6 and IGHJ4 were used in 9 (45%) and 6 (30%) clones, respectively. In 6 out of 20 (30%) IGH rearranged sequences, CDR3 was in frame whereas 14 (70%) had rearranged sequences and CDR3 was out of frame. A somatic mutation in Vmut/Dmut/Jmut was detected in 14 of 20 IGH sequences. On average, Vmut/Dmut/Jmut were detected in 0.1 nt, 1.1 nt, and 0.2 nt, respectively.
  
  
  CONCLUSIONS
  The IGHV3 gene was frequently used whereas lower frequencies of IGHV5 and IGHV6 and a higher frequency of IGHV4 were detected in children compared with young adults. The IGHD2 and IGHD3 genes were over-represented, and the IGHJ6 gene was predominantly used in precursor-B-ALL. However, the IGH gene rearrangements in precursor-B-ALL did not show any significant age-associated genotype pattern attributed to our population.
authors.affiliation: Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India.; Department of Biotechnology, Dr. M.G.R. Educational & Research Institute, Chennai, India.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Sudhakar
authors.affiliation: Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India.
authors.forename: Thangarajan
authors.initials: T
authors.lastname: Rajkumar
authors.affiliation: Department of Hematology and Immunology, Cancer Institute (WIA), Chennai, India.
authors.forename: Kamalalayam Raghavan
authors.initials: KR
authors.lastname: Rajalekshmy
authors.affiliation: Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India.
authors.forename: Nirmala Karunakaran
authors.initials: NK
authors.lastname: Nancy
keywords: Gene rearrangements; Immunoglobulin heavy(IGH); Precursor B-ALL; V-D-J