Genomic Imbalances Are Confined to Non-Proliferating Cells in Paediatric Patients with Acute Myeloid Leukaemia and a Normal or Incomplete Karyotype

被引：2

作者：

Ballabio, Erica ^{[1
,2
,3
]}

Regan, Regina ^{[4
,5
]}

Garimberti, Elisa ^{[1
,2
]}

Harbott, Jochen ^{[6
]}

Bradtke, Jutta ^{[6
]}

Teigler-Schlegel, Andrea ^{[6
]}

Biondi, Andrea ^{[7
]}

Cazzaniga, Giovanni ^{[7
]}

Giudici, Giovanni ^{[7
]}

Wainscoat, James S. ^{[3
]}

Boultwood, Jacqueline ^{[3
]}

Bridger, Joanna M. ^{[1
,2
]}

Knight, Samantha J. L. ^{[4
,5
]}

Tosi, Sabrina ^{[1
,2
]}

机构：

[1] Brunel Univ, Ctr Cell & Chromosome Biol, London, England

[2] Brunel Univ, Brunel Inst Canc Genet & Pharmacogen, Div Biosci, London, England

[3] John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, LRF Mol Haematol Unit, Oxford OX3 9DU, England

[4] NIHR Biomed Res Ctr, Oxford, England

[5] Wellcome Trust Ctr Human Genet, Oxford, England

[6] Univ Giessen, Dept Paediat Haematol & Oncol, Oncogenet Lab, Giessen, Germany

[7] Clin Pediat Univ Milano Bicocca, Ctr Ric Tettamanti, Monza, Italy

来源：

PLOS ONE | 2011年 / 6卷 / 06期

基金：

英国惠康基金;

关键词：

IN-SITU HYBRIDIZATION; COPY NUMBER ALTERATIONS; NORMAL CYTOGENETICS; YOUNGER ADULTS; ONCOLOGY-GROUP; MUTATIONS; AML; ABNORMALITIES; ABERRATIONS; CANCER;

D O I：

10.1371/journal.pone.0020607

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Leukaemia is often associated with genetic alterations such as translocations, amplifications and deletions, and recurrent chromosome abnormalities are used as markers of diagnostic and prognostic relevance. However, a proportion of acute myeloid leukaemia (AML) cases have an apparently normal karyotype despite comprehensive cytogenetic analysis. Based on conventional cytogenetic analysis of banded chromosomes, we selected a series of 23 paediatric patients with acute myeloid leukaemia and performed whole genome array comparative genome hybridization (aCGH) using DNA samples derived from the same patients. Imbalances involving large chromosomal regions or entire chromosomes were detected by aCGH in seven of the patients studied. Results were validated by fluorescence in situ hybridization (FISH) to both interphase nuclei and metaphase chromosomes using appropriate bacterial artificial chromosome (BAC) probes. The majority of these copy number alterations (CNAs) were confirmed by FISH and found to localize to the interphase rather than metaphase nuclei. Furthermore, the proliferative states of the cells analyzed by FISH were tested by immunofluorescence using an antibody against the proliferation marker pKi67. Interestingly, these experiments showed that, in the vast majority of cases, the changes appeared to be confined to interphase nuclei in a non-proliferative status.

引用

页数：9