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Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype.

Intratumor genetic heterogeneity is a key mechanism underlying tumor progression and therapeutic resistance. The prevailing model for explaining intratumor diversity, the clonal evolution model, has recently been challenged by proponents of the cancer stem cell hypothesis. To investigate this issue,... Full description

Journal Title: The Journal of clinical investigation February 2010, Vol.120(2), pp.636-644
Main Author: Park, So Yeon
Other Authors: Gönen, Mithat , Kim, Hee Jung , Michor, Franziska , Polyak, Kornelia
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1558-8238 ; DOI: 10.1172/JCI40724
Link: http://search.proquest.com/docview/733146631/?pq-origsite=primo
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title: Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype.
format: Article
creator:
  • Park, So Yeon
  • Gönen, Mithat
  • Kim, Hee Jung
  • Michor, Franziska
  • Polyak, Kornelia
subjects:
  • Antigens, CD–Analysis
  • Breast Neoplasms–Genetics
  • Cell Differentiation–Pathology
  • Chromosomes, Human, Pair 8–Analysis
  • Disease Progression–Analysis
  • Female–Analysis
  • Genes, Erbb-2–Analysis
  • Genetic Variation–Analysis
  • Humans–Analysis
  • Hyaluronan Receptors–Analysis
  • In Situ Hybridization, Fluorescence–Analysis
  • Neoplasm Invasiveness–Analysis
  • Receptors, Ige–Analysis
  • Abridged
  • Antigens, CD
  • Hyaluronan Receptors
  • Receptors, Ige
ispartof: The Journal of clinical investigation, February 2010, Vol.120(2), pp.636-644
description: Intratumor genetic heterogeneity is a key mechanism underlying tumor progression and therapeutic resistance. The prevailing model for explaining intratumor diversity, the clonal evolution model, has recently been challenged by proponents of the cancer stem cell hypothesis. To investigate this issue, we performed combined analyses of markers associated with cellular differentiation states and genotypic alterations in human breast carcinomas and evaluated diversity with ecological and evolutionary methods. Our analyses showed a high degree of genetic heterogeneity both within and between distinct tumor cell populations that were defined based on markers of cellular phenotypes including stem cell-like characteristics. In several tumors, stem cell-like and more-differentiated cancer cell populations were genetically distinct, leading us to question the validity of a simple differentiation hierarchy-based cancer stem cell model. The degree of diversity correlated with clinically relevant breast tumor subtypes and in some tumors was markedly different between the in situ and invasive cell populations. We also found that diversity measures were associated with clinical variables. Our findings highlight the importance of genetic diversity in intratumor heterogeneity and the value of analyzing tumors as distinct populations of cancer cells to more effectively plan treatments.
language: eng
source:
identifier: E-ISSN: 1558-8238 ; DOI: 10.1172/JCI40724
fulltext: fulltext
issn:
  • 15588238
  • 1558-8238
url: Link


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titleCellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype.
creatorPark, So Yeon ; Gönen, Mithat ; Kim, Hee Jung ; Michor, Franziska ; Polyak, Kornelia
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identifierE-ISSN: 1558-8238 ; DOI: 10.1172/JCI40724
subjectAntigens, CD–Analysis ; Breast Neoplasms–Genetics ; Cell Differentiation–Pathology ; Chromosomes, Human, Pair 8–Analysis ; Disease Progression–Analysis ; Female–Analysis ; Genes, Erbb-2–Analysis ; Genetic Variation–Analysis ; Humans–Analysis ; Hyaluronan Receptors–Analysis ; In Situ Hybridization, Fluorescence–Analysis ; Neoplasm Invasiveness–Analysis ; Receptors, Ige–Analysis ; Abridged ; Antigens, CD ; Hyaluronan Receptors ; Receptors, Ige
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descriptionIntratumor genetic heterogeneity is a key mechanism underlying tumor progression and therapeutic resistance. The prevailing model for explaining intratumor diversity, the clonal evolution model, has recently been challenged by proponents of the cancer stem cell hypothesis. To investigate this issue, we performed combined analyses of markers associated with cellular differentiation states and genotypic alterations in human breast carcinomas and evaluated diversity with ecological and evolutionary methods. Our analyses showed a high degree of genetic heterogeneity both within and between distinct tumor cell populations that were defined based on markers of cellular phenotypes including stem cell-like characteristics. In several tumors, stem cell-like and more-differentiated cancer cell populations were genetically distinct, leading us to question the validity of a simple differentiation hierarchy-based cancer stem cell model. The degree of diversity correlated with clinically relevant breast tumor subtypes and in some tumors was markedly different between the in situ and invasive cell populations. We also found that diversity measures were associated with clinical variables. Our findings highlight the importance of genetic diversity in intratumor heterogeneity and the value of analyzing tumors as distinct populations of cancer cells to more effectively plan treatments.
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