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本帖最后由 饶冠华 于 2011-1-20 17:17 编辑
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Cells of origin in cancer
q9 t+ R6 r4 N# O( v; Y: JJane E. Visvader
: v8 U. R ]/ O/ t" q9 {0 ~5 {: E* }Journal name: Nature : o4 ]( q* n& H1 w2 X1 o
Volume: 469,
# @/ _! V% I! x1 ]7 o! J, D# nPages: 314–322 % C/ c0 r: c* K; e' D
Date published: (20 January 2011) ! [" o2 ]; D/ |
DOI: doi:10.1038/nature09781 ( \4 ?/ o! N6 K1 e: E% y- i9 E- F
Published online 19 January 2011 ' }! w+ \2 j- T$ {) W
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Both solid tumours and leukaemias show considerable histological and functional heterogeneity. It is widely accepted that genetic lesions have a major role in determining tumour phenotype, but evidence is also accumulating that cancers of distinct subtypes within an organ may derive from different 'cells of origin'. These cells acquire the first genetic hit or hits that culminate in the initiation of cancer. The identification of these crucial target cell populations may allow earlier detection of malignancies and better prediction of tumour behaviour, and ultimately may lead to preventive therapies for individuals at high risk of developing cancer.
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同期另一篇aritcle
% {6 R# A& p; V: X; c+ ^1 bNature. 2010 Dec 15. [Epub ahead of print]
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Genetic variegation of clonal architecture and propagating cells in leukaemia.5 ]) M# I, E" R3 r8 S( p, G9 [
Anderson K, Lutz C, van Delft FW, Bateman CM, Guo Y, Colman SM, Kempski H, Moorman AV, Titley I, Swansbury J, Kearney L, Enver T, Greaves M.6 l. I& g. g e y( D7 l
! z) H5 q; m- b% M- T8 eSection of Haemato-Oncology, The Institute of Cancer Research, Sutton SM2 5NG, UK.
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Abstract
$ V0 m4 Y1 |% \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 IL2Rγ(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.
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$ o; c( {; L4 ]- ]9 GPMID: 21160474 [PubMed - as supplied by publisher]
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发表于 2011-1-20 17:12
发表于 2011-1-20 20:19
发表于 2011-3-12 07:49
