Cancer stem cells with genetic instability: the best vehicle with the best engine for cancer

Lagasse, Eric

doi:10.1038/sj.gt.3303068

Cited by 79 publications

(53 citation statements)

References 67 publications

(72 reference statements)

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“…[27][28][29] Nonrandom genomic alterations associated with dedifferentiation have also been reported in dedifferentiated chondrosarcomas 30 and liposarcomas 31 and, in the latter, specific copy-number abnormalities are associated with a distinct morphology and poor prognosis.…”

Section: Discussionmentioning

confidence: 97%

Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation

et al. 2015

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Solitary fibrous tumors, which are characterized by their broad morphological spectrum and unpredictable behavior, are rare mesenchymal neoplasias that are currently divided into three main variants that have the NAB2-STAT6 gene fusion as their unifying molecular lesion: usual, malignant and dedifferentiated solitary fibrous tumors. The aims of this study were to validate molecular and immunohistochemical/biochemical approaches to diagnose the range of solitary fibrous tumors by focusing on the dedifferentiated variant, and to reveal the genetic events associated with dedifferentiation by integrating the findings of array comparative genomic hybridization. We studied 29 usual, malignant and dedifferentiated solitary fibrous tumors from 24 patients (including paired samples from five patients whose tumors progressed to the dedifferentiated form) by means of STAT6 immunohistochemistry and (when frozen material was available) reverse-transcriptase polymerase chain reaction and biochemistry. In addition, the array comparative genomic hybridization findings were used to profile 12 tumors from nine patients. The NAB2/STAT6 fusion was detected in all of the tumors, but immunohistochemistry and western blotting indicated that chimeric protein expression was atypical or absent in 9 out of 11 dedifferentiated tumors. The comparative genomic hybridization results revealed that the usual and malignant solitary fibrous tumors had a simple profile, whereas the genome of the dedifferentiated tumors was complex and unstable, and suggested that 13q and 17p deletions and TP53 mutations may be present in malignant lesions before the full expression of a dedifferentiated phenotype. Solitary fibrous tumor dedifferentiation is associated with the loss of chimeric oncoprotein expression, genomic instability, and cell decommitment and reprogramming. The assessment of dedifferentiated solitary fibrous tumors is based on the presence of the fusion transcripts and, in principle, negative STAT6 immunohistochemistry should not rule out a diagnosis of solitary fibrous tumor. Modern Pathology (2015Pathology ( ) 28, 1074Pathology ( -1083 doi:10.1038/modpathol.2015 published online 29 May 2015 Solitary fibrous tumors are rare mesenchymal tumors (incidence o 1 per million) that were originally described on the pleurae but have subsequently been recognized at virtually all body sites. 1 The current classification includes usual, malignant and the recently described dedifferentiated variants. [1][2][3] The morphobiological features distinguishing the malignant and usual variants are hypercellularity, cell pleomorphism, necrosis and a mitotic index of 44/10 high-power fields. However,

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Section: Discussionmentioning

confidence: 97%

Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation

et al. 2015

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“…Following treatment, SC normally remain inactive for some time; however the change in the tumour microenvironment along with acquired genetic transformations that occur after initial treatment may later trigger the development of a more aggressive SC phenotype (56). In well differentiated thyroid cancers, often tumour cells demonstrate sensitivity towards initial radioactive iodine treatment.…”

Section: Discussionmentioning

confidence: 99%

Thyroid Stem Cells: Concept and Clinical Implications

Latar

Mahkamova²,

Aspinall³

et al. 2016

JSA

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Thyroid pathology is the commonest endocrine surgical problem encountered. However, the study of thyroid stem cells is relatively new in the field of stem cell research. Since the identification of thyroid stem cells in 1992, research interest in this area has been increasing mainly based on furthering our knowledge of the biology of these important cells that are thought to be responsible for tumourigenesis and propagation of cancers. This article reviews the current science and biology of thyroid stem cells and summarizes their potential role in the general management of thyroid disorders.

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“…How does genomic instability contribute to the transformation of normal stem cells? It has been suggested that normal stem cells and their cellular pathways may acquire stochastic malignant ability (Lagasse, 2008). Clark and colleagues generated highly metastatic cancer stem cells by implantation of murine embryonic germ cells (EGCs) into the testes of adult severe combined immune deficiency (SCID) mice (Conway et al, 2009).…”

Section: Genomic Instability As a Driving Force For Transforming Normmentioning

confidence: 99%

Connections between Genomic Instability and Cancer Stem Cells

Li¹,

Borodyansky²,

Yang³

2011

Cancer Stem Cells Theories and Practice

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Cancer stem cells with genetic instability: the best vehicle with the best engine for cancer

Cited by 79 publications

References 67 publications

Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation

Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation

Thyroid Stem Cells: Concept and Clinical Implications

Connections between Genomic Instability and Cancer Stem Cells

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