2012
DOI: 10.1126/scitranslmed.3003854
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Intratumor Heterogeneity: Seeing the Wood for the Trees

Abstract: Intratumor genetic heterogeneity impedes development of new therapeutics and biomarkers that predict drug response.

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Cited by 465 publications
(405 citation statements)
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References 29 publications
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“…Using microdiversity to obtain actionable clinical information is a novel concept. It provides a stark contrast to current strategies for biomarker evaluation, with mutation status, genome profile or protein expression typically being evaluated in merely a single tumour sample-resting on the assumption that tumours are biologically homogeneous 5 . Microdiversity would be a particularly attractive clinical marker as it is a parameter possible to quantify using standard genome arrays and relatively simple bioinformatic operations 17 .…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Using microdiversity to obtain actionable clinical information is a novel concept. It provides a stark contrast to current strategies for biomarker evaluation, with mutation status, genome profile or protein expression typically being evaluated in merely a single tumour sample-resting on the assumption that tumours are biologically homogeneous 5 . Microdiversity would be a particularly attractive clinical marker as it is a parameter possible to quantify using standard genome arrays and relatively simple bioinformatic operations 17 .…”
Section: Discussionmentioning
confidence: 99%
“…Such genetic intra-and intertumoral heterogeneity is clinically significant, as it confounds the analysis of biomarkers based on single tumour samples. To what extent it also has a direct impact on treatment response and progression of tumour disease has remained unclear [5][6][7] . It is also largely unknown whether the high degree of genetic variation observed in the common adult cancers [1][2][3][4] is also present in tumours from infants and children.…”
mentioning
confidence: 99%
“…In cancer, it is usually observed that the tumors acquire more mutations with disease progression, and emerging evidence suggests that genetic abnormalities vary substantially between metastases or even within a single tumor mass, indicating intra-tumor heterogeneity. [12][13][14] Determining the impact of such clonal structures still requires future studies. Intra-tumoral heterogeneity has important consequences for personalizedmedicine approaches.…”
Section: Discussionmentioning
confidence: 99%
“…Some researchers have suggested that the heterogeneity in cancer growth follows a Darwinian evolutionary theory of natural selection [12], whilst others have concluded that there are two plausible origins of diversity in tumour cells expansion, described by the 'clonal evolution' theory and the 'cancer stem cell' theory. [13][14][15] The clonal evolution theory (cancer monoclonality) presupposes that tumour cells result from a solitary clone of mitotically unstable cell that differentiate into different offspring lineage clones that have developed additional unique genetic damage down the lineage.…”
Section: Diagnostic Inaccuracies In Colorectal Cancermentioning
confidence: 99%