PMID- 21160474
OWN - NLM
STAT- MEDLINE
DCOM- 20110217
LR  - 20220309
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Linking)
VI  - 469
IP  - 7330
DP  - 2011 Jan 20
TI  - Genetic variegation of clonal architecture and propagating cells in leukaemia.
PG  - 356-61
LID - 10.1038/nature09650 [doi]
AB  - Little is known of the genetic architecture of cancer at the subclonal and 
      single-cell level or in the cells responsible for cancer clone maintenance and 
      propagation. Here we have examined this issue in childhood acute lymphoblastic 
      leukaemia in which the ETV6-RUNX1 gene fusion is an early or initiating genetic 
      lesion followed by a modest number of recurrent or 'driver' copy number 
      alterations. By multiplexing fluorescence in situ hybridization probes for these 
      mutations, up to eight genetic abnormalities can be detected in single cells, a 
      genetic signature of subclones identified and a composite picture of subclonal 
      architecture and putative ancestral trees assembled. Subclones in acute 
      lymphoblastic leukaemia have variegated genetics and complex, nonlinear or 
      branching evolutionary histories. Copy number alterations are independently and 
      reiteratively acquired in subclones of individual patients, and in no 
      preferential order. Clonal architecture is dynamic and is subject to change in 
      the lead-up to a diagnosis and in relapse. Leukaemia propagating cells, assayed 
      by serial transplantation in NOD/SCID IL2Rgamma(null) mice, are also genetically 
      variegated, mirroring subclonal patterns, and vary in competitive regenerative 
      capacity in vivo. These data have implications for cancer genomics and for the 
      targeted therapy of cancer.
FAU - Anderson, Kristina
AU  - Anderson K
AD  - Section of Haemato-Oncology, The Institute of Cancer Research, Sutton SM2 5NG, 
      UK.
FAU - Lutz, Christoph
AU  - Lutz C
FAU - van Delft, Frederik W
AU  - van Delft FW
FAU - Bateman, Caroline M
AU  - Bateman CM
FAU - Guo, Yanping
AU  - Guo Y
FAU - Colman, Susan M
AU  - Colman SM
FAU - Kempski, Helena
AU  - Kempski H
FAU - Moorman, Anthony V
AU  - Moorman AV
FAU - Titley, Ian
AU  - Titley I
FAU - Swansbury, John
AU  - Swansbury J
FAU - Kearney, Lyndal
AU  - Kearney L
FAU - Enver, Tariq
AU  - Enver T
FAU - Greaves, Mel
AU  - Greaves M
LA  - eng
SI  - GEO/GSE24412
GR  - MC_U137973817/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101215
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (Il2rg protein, mouse)
RN  - 0 (Interleukin Receptor Common gamma Subunit)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (TEL-AML1 fusion protein)
SB  - IM
CIN - Cell Stem Cell. 2011 Mar 4;8(3):242-4. PMID: 21362561
MH  - Animals
MH  - Clone Cells/metabolism/*pathology
MH  - Core Binding Factor Alpha 2 Subunit
MH  - DNA Copy Number Variations/genetics
MH  - DNA Mutational Analysis
MH  - Disease Progression
MH  - Genetic Variation/*genetics
MH  - Genotype
MH  - Humans
MH  - Immunophenotyping
MH  - In Situ Hybridization, Fluorescence
MH  - Interleukin Receptor Common gamma Subunit/deficiency/genetics
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Neoplasm Transplantation
MH  - Oncogene Proteins, Fusion/genetics
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics/*pathology
EDAT- 2010/12/17 06:00
MHDA- 2011/02/18 06:00
CRDT- 2010/12/17 06:00
PHST- 2010/05/20 00:00 [received]
PHST- 2010/10/27 00:00 [accepted]
PHST- 2010/12/17 06:00 [entrez]
PHST- 2010/12/17 06:00 [pubmed]
PHST- 2011/02/18 06:00 [medline]
AID - nature09650 [pii]
AID - 10.1038/nature09650 [doi]
PST - ppublish
SO  - Nature. 2011 Jan 20;469(7330):356-61. doi: 10.1038/nature09650. Epub 2010 Dec 15.