title: A high complex karyotype involving eleven chromosomes including three novel chromosomal aberrations and monoallelic loss ofTP53in case of follicular lymphoma transformed into B-cell lymphoblastic leukemia.
abstract: BACKGROUND
  Follicular lymphoma (FL) is one of the most common B-cell non-Hodgkin's lymphoma (NHL). A subset of FL cases transform into more aggressive malignancies, most often to diffuse large B-cell lymphoma (DLBCL); in addition, lymphoblastic lymphoma and acute lymphoblastic leukemia (ALL) have also been rarely reported. The most common cytogenetic abnormalities associated with FL are translocation t(14;18)(q32;q21) withBCL2rearrangements, present in 80-90% of all FL. However, that translocation alone is insufficient to cause FL and additional genomic events specifically leading to this kind of disease are still to be determined. The most frequently reported secondary changes are gains of chromosomes 7p or 7q, Xp, 12q and 18q, as well as losses on 6q and mutations withinBCL2and/orBCL6genes. The presence of additional genomic aberrations, in particular 17p and 6q deletions is more frequent in grade 2 and 3 FL patients and correlated with shorter survival and a higher rate of transformation into DLBCL.
  
  
  METHODS
  We describe here, an adult FL grade 2 patient that had transformed to B-ALL at diagnosis. Banding cytogenetics, refined by multi-color fluorescence in situ hybridization including array-proven multicolor banding revealed a unique complex karyotype involving eleven chromosomes, translocation t(X;20)(p21.3;q11.2), translocation t(3;20)(q26.2;q12), and a dicentric dic(17;18). Interestingly, the dicentric chromosome led to monosomy of the tumor suppressor gene TP53. The case had an immunophenotype consistent with follicular center cell lymphoma according to the World Health Organization (WHO) recommendations.
  
  
  CONCLUSIONS
  To the best of our knowledge, a comparable adult FL grade 2 case that transformed to B-ALL associated with such a complex karyotype and loss ofTP53was not previously reported. Most of complex aberrations were found simultaneously in approximately 85% of studied malignant cells and the remained cells studied were non-clonal; mechanisms explaining this may be either multiple-step mechanisms or single step in sense of chromothripsis.
  
  
  BACKGROUND
  Identifying number: 3842. Registered 09 July 2012.
authors.affiliation: Human Genetics Division, Department of Molecular Biology and Biotechnology, Atomic Energy Commission of Syria, P.O. Box 6091, Damascus, Syria.
authors.forename: Abdulsamad
authors.initials: A
authors.lastname: Wafa
authors.affiliation: Human Genetics Division, Department of Molecular Biology and Biotechnology, Atomic Energy Commission of Syria, P.O. Box 6091, Damascus, Syria.
authors.forename: Faten
authors.initials: F
authors.lastname: Moassass
authors.affiliation: Jena University Hospital, Institute of Human Genetics, Kollegiengasse 10, D-07743 Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.affiliation: Jena University Hospital, Institute of Human Genetics, Kollegiengasse 10, D-07743 Jena, Germany.
authors.forename: Samarth
authors.initials: S
authors.lastname: Bhatt
authors.affiliation: Molecular Biology and Biotechnology Department, Mammalians Biology Division, Flow-cytometry Laboratory, Atomic Energy Commission of Syria, P.O. Box 6091 Damascus, Syria.
authors.forename: Abdulmunim
authors.initials: A
authors.lastname: Aljapawe
authors.affiliation: Human Genetics Division, Department of Molecular Biology and Biotechnology, Atomic Energy Commission of Syria, P.O. Box 6091, Damascus, Syria.
authors.forename: Walid
authors.initials: W
authors.lastname: Al Achkar
keywords: Chromosomal aberration; Clonal evolution; FISH; Follicular lymphoma (FL); Prognostic factors; t(14;18)(q32;q21)