Recurrent chromosome abnormalities define nonoverlapping unique subgroups of tumors in patients with chronic lymphocytic leukemia and known karyotypic abnormalities

Victor H. Jimenez-Zepeda, Wee Joo Chng, Roelandt F J Schop, Esteban D Braggio, Jose F. Leis, Neil Elliot Kay, Rafael Fonseca

Research output: Contribution to journalArticle

1 Citation (Scopus)

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. Material and 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. Conclusion: 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).

Original languageEnglish (US)
Pages (from-to)467-476
Number of pages10
JournalClinical Lymphoma, Myeloma and Leukemia
Volume13
Issue number4
DOIs
StatePublished - Aug 2013

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
Chromosome Aberrations
Neoplasms
Chromosomes, Human, 13-15
Cyclin D2
Biological Evolution
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase 2
Cyclin D
Abnormal Karyotype
Genetic Models
Trisomy
Hematologic Neoplasms
Karyotype
Cytogenetics
Genetic Therapy
Disease Progression
Clone Cells
Chromosomes
Observation

Keywords

  • Chromosome banding analysis
  • Chronic lymphocytic leukemia (CLL)
  • del(13q)
  • Trisomy 12

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Recurrent chromosome abnormalities define nonoverlapping unique subgroups of tumors in patients with chronic lymphocytic leukemia and known karyotypic abnormalities. / Jimenez-Zepeda, Victor H.; Chng, Wee Joo; Schop, Roelandt F J; Braggio, Esteban D; Leis, Jose F.; Kay, Neil Elliot; Fonseca, Rafael.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 13, No. 4, 08.2013, p. 467-476.

Research output: Contribution to journalArticle

@article{a5118dd9c5a7431193f22324f83c6481,
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. Material and 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. Conclusion: 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).",
keywords = "Chromosome banding analysis, Chronic lymphocytic leukemia (CLL), del(13q), Trisomy 12",
author = "Jimenez-Zepeda, {Victor H.} and Chng, {Wee Joo} and Schop, {Roelandt F J} and Braggio, {Esteban D} and Leis, {Jose F.} and Kay, {Neil Elliot} and Rafael Fonseca",
year = "2013",
month = "8",
doi = "10.1016/j.clml.2013.05.003",
language = "English (US)",
volume = "13",
pages = "467--476",
journal = "Clinical Lymphoma, Myeloma and Leukemia",
issn = "2152-2669",
publisher = "Cancer Media Group",
number = "4",

}

TY - JOUR

T1 - Recurrent chromosome abnormalities define nonoverlapping unique subgroups of tumors in patients with chronic lymphocytic leukemia and known karyotypic abnormalities

AU - Jimenez-Zepeda, Victor H.

AU - Chng, Wee Joo

AU - Schop, Roelandt F J

AU - Braggio, Esteban D

AU - Leis, Jose F.

AU - Kay, Neil Elliot

AU - Fonseca, Rafael

PY - 2013/8

Y1 - 2013/8

N2 - 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. Material and 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. Conclusion: 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).

AB - 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. Material and 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. Conclusion: 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).

KW - Chromosome banding analysis

KW - Chronic lymphocytic leukemia (CLL)

KW - del(13q)

KW - Trisomy 12

UR - http://www.scopus.com/inward/record.url?scp=84880755093&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880755093&partnerID=8YFLogxK

U2 - 10.1016/j.clml.2013.05.003

DO - 10.1016/j.clml.2013.05.003

M3 - Article

C2 - 23876845

AN - SCOPUS:84880755093

VL - 13

SP - 467

EP - 476

JO - Clinical Lymphoma, Myeloma and Leukemia

JF - Clinical Lymphoma, Myeloma and Leukemia

SN - 2152-2669

IS - 4

ER -