title: Recurrent chromosome abnormalities define nonoverlapping unique subgroups of tumors in patients with chronic lymphocytic leukemia and known karyotypic abnormalities.
abstract: BACKGROUND
  A major conclusion drawn from the accumulated cytogenetic data on solid tumors and some hematologic malignancies is that tumors progress by the acquisition of chromosomal changes, as reflected by more aggressive tumors containing a larger number of chromosomal abnormalities. An additional observation is that some chromosomal changes appear early in the disease progression, and some others appear late.
  
  
  METHODS
  On the basis of this information, a model for karyotypic evolution in chronic lymphocytic leukemia (CLL) is presented. The Mitelman Database of Chromosomes in Cancer was searched, and 1749 abnormal karyotypes were assessed. The main clones were analyzed, and chromosomal gains and losses were used to design a model of genetic acquisition based on the calculation of a variable called time to occurrence (TO).
  
  
  RESULTS
  Our comprehensive study of genetic abnormalities in a large number of CLL karyotypes revealed that most CLL has 2 chromosomal aberrations at diagnosis. Moreover, the temporal analysis suggests that trisomy 12 is an early event in the biological evolution of CLL.
  
  
  CONCLUSIONS
  These results highlight the possibility of targeted therapies affecting the genes located on this chromosome (cyclin D, cyclin D2, cyclin-dependent kinase 2, and cyclin-dependent kinase 4).
authors.affiliation: Mayo Clinic Cancer Center, Scottsdale, AZ, USA.
authors.forename: Victor H
authors.initials: VH
authors.lastname: Jimenez-Zepeda
authors.forename: Wee Joo
authors.initials: WJ
authors.lastname: Chng
authors.forename: Roelandt F J
authors.initials: RF
authors.lastname: Schop
authors.forename: Esteban
authors.initials: E
authors.lastname: Braggio
authors.forename: Jose F
authors.initials: JF
authors.lastname: Leis
authors.forename: Neil
authors.initials: N
authors.lastname: Kay
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002881:Chromosomes, Human, Pair 12; D002882:Chromosomes, Human, Pair 13; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D003582:Cytogenetics; D018450:Disease Progression; D005260:Female; D023281:Genomics; D006801:Humans; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000145:classification* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014178:Translocation, Genetic; D014314:Trisomy
keywords: Chromosome banding analysis; Chronic lymphocytic leukemia (CLL); Trisomy 12; del(13q)