PittsburghV1, Main, Exploration, bibRecord, 002920

Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer

Identifieur interne : 002920 ( Main/Exploration ); précédent : 002919; suivant : 002921

Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer

Auteurs : Lindsey M. Kelly ; Guillermo Barila ; Pengyuan Liu ; Viktoria N. Evdokimova ; Sumita Trivedi ; Federica Panebianco ; Manoj Gandhi ; Sally E. Carty ; Steven P. Hodak ; Jianhua Luo ; Sanja Dacic ; Yan P. Yu ; Marina N. Nikiforova ; Robert L. Ferris ; Daniel L. Altschuler ; Yuri E. Nikiforov

Source :

Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2014.

RBID : PMC:3964116

Descripteurs français

English descriptors

KwdEn :
- Base Sequence, Blotting, Western, Calmodulin-Binding Proteins (genetics), Gene Fusion (genetics), HEK293 Cells, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Membrane Proteins (genetics), Molecular Sequence Data, Nerve Tissue Proteins (genetics), Pyrazoles, Pyridines, Pyrimidines, Real-Time Polymerase Chain Reaction, Receptor Protein-Tyrosine Kinases (antagonists & inhibitors), Receptor Protein-Tyrosine Kinases (genetics), Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, RNA, Thyroid Neoplasms (genetics), Transcriptome (genetics).
MESH :
- chemical , antagonists & inhibitors : Receptor Protein-Tyrosine Kinases.
- chemical , genetics : Calmodulin-Binding Proteins, Membrane Proteins, Nerve Tissue Proteins, Receptor Protein-Tyrosine Kinases.
- genetics : Gene Fusion, Thyroid Neoplasms, Transcriptome.
- Base Sequence, Blotting, Western, HEK293 Cells, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Molecular Sequence Data, Pyrazoles, Pyridines, Pyrimidines, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, RNA.

Abstract

Significance

Thyroid cancer is common and has an excellent outcome in many cases, although a proportion of these tumors have a progressive clinical course and high mortality. Using whole-transcriptome (RNA-sequencing) analysis, we discovered previously unknown genetic events, anaplastic lymphoma kinase (ALK) gene fusions, in thyroid cancer and demonstrate that they occur more often in aggressive cancers. The most common fusion identified in these tumors involved the striatin (STRN) gene, and we show that it is transforming and tumorigenic in vivo. Finally, we demonstrate that the kinase activity of STRN-ALK can be blocked by ALK inhibitors, raising a possibility that ALK fusions may be used as a therapeutic target for patients with the most aggressive and frequently lethal forms of thyroid cancer.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964116

DOI: 10.1073/pnas.1321937111
PubMed: 24613930
PubMed Central: 3964116

Affiliations:

Le document en format XML

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</affiliation>
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</affiliation>
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<term>Gene Fusion (genetics)</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Immunohistochemistry</term>
<term>In Situ Hybridization, Fluorescence</term>
<term>Membrane Proteins (genetics)</term>
<term>Molecular Sequence Data</term>
<term>Nerve Tissue Proteins (genetics)</term>
<term>Pyrazoles</term>
<term>Pyridines</term>
<term>Pyrimidines</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Receptor Protein-Tyrosine Kinases (antagonists & inhibitors)</term>
<term>Receptor Protein-Tyrosine Kinases (genetics)</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
<term>Sequence Analysis, RNA</term>
<term>Thyroid Neoplasms (genetics)</term>
<term>Transcriptome (genetics)</term>
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<term>Cellules HEK293</term>
<term>Données de séquences moléculaires</term>
<term>Fusion de gènes (génétique)</term>
<term>Humains</term>
<term>Immunohistochimie</term>
<term>Protéines de liaison à la calmoduline (génétique)</term>
<term>Protéines de tissu nerveux (génétique)</term>
<term>Protéines membranaires (génétique)</term>
<term>Pyrazoles</term>
<term>Pyridines</term>
<term>Pyrimidines</term>
<term>RT-PCR</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Récepteurs à activité tyrosine kinase (antagonistes et inhibiteurs)</term>
<term>Récepteurs à activité tyrosine kinase (génétique)</term>
<term>Séquence nucléotidique</term>
<term>Technique FISH</term>
<term>Technique de Western</term>
<term>Transcriptome (génétique)</term>
<term>Tumeurs de la thyroïde (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Receptor Protein-Tyrosine Kinases</term>
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<term>Nerve Tissue Proteins</term>
<term>Receptor Protein-Tyrosine Kinases</term>
</keywords>
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</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Gene Fusion</term>
<term>Thyroid Neoplasms</term>
<term>Transcriptome</term>
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<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Fusion de gènes</term>
<term>Protéines de liaison à la calmoduline</term>
<term>Protéines de tissu nerveux</term>
<term>Protéines membranaires</term>
<term>Récepteurs à activité tyrosine kinase</term>
<term>Transcriptome</term>
<term>Tumeurs de la thyroïde</term>
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<term>Blotting, Western</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Immunohistochemistry</term>
<term>In Situ Hybridization, Fluorescence</term>
<term>Molecular Sequence Data</term>
<term>Pyrazoles</term>
<term>Pyridines</term>
<term>Pyrimidines</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
<term>Sequence Analysis, RNA</term>
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<term>Données de séquences moléculaires</term>
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<term>Pyrazoles</term>
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<front><div type="abstract" xml:lang="en"><title>Significance</title>
<p>Thyroid cancer is common and has an excellent outcome in many cases, although a proportion of these tumors have a progressive clinical course and high mortality. Using whole-transcriptome (RNA-sequencing) analysis, we discovered previously unknown genetic events, anaplastic lymphoma kinase (<italic>ALK</italic>
) gene fusions, in thyroid cancer and demonstrate that they occur more often in aggressive cancers. The most common fusion identified in these tumors involved the striatin (<italic>STRN</italic>
) gene, and we show that it is transforming and tumorigenic in vivo. Finally, we demonstrate that the kinase activity of STRN-ALK can be blocked by ALK inhibitors, raising a possibility that ALK fusions may be used as a therapeutic target for patients with the most aggressive and frequently lethal forms of thyroid cancer.</p>
</div>
</front>
</TEI>
<affiliations><list></list>
<tree><noCountry><name sortKey="Altschuler, Daniel L" sort="Altschuler, Daniel L" uniqKey="Altschuler D" first="Daniel L." last="Altschuler">Daniel L. Altschuler</name>
<name sortKey="Barila, Guillermo" sort="Barila, Guillermo" uniqKey="Barila G" first="Guillermo" last="Barila">Guillermo Barila</name>
<name sortKey="Carty, Sally E" sort="Carty, Sally E" uniqKey="Carty S" first="Sally E." last="Carty">Sally E. Carty</name>
<name sortKey="Dacic, Sanja" sort="Dacic, Sanja" uniqKey="Dacic S" first="Sanja" last="Dacic">Sanja Dacic</name>
<name sortKey="Evdokimova, Viktoria N" sort="Evdokimova, Viktoria N" uniqKey="Evdokimova V" first="Viktoria N." last="Evdokimova">Viktoria N. Evdokimova</name>
<name sortKey="Ferris, Robert L" sort="Ferris, Robert L" uniqKey="Ferris R" first="Robert L." last="Ferris">Robert L. Ferris</name>
<name sortKey="Gandhi, Manoj" sort="Gandhi, Manoj" uniqKey="Gandhi M" first="Manoj" last="Gandhi">Manoj Gandhi</name>
<name sortKey="Hodak, Steven P" sort="Hodak, Steven P" uniqKey="Hodak S" first="Steven P." last="Hodak">Steven P. Hodak</name>
<name sortKey="Kelly, Lindsey M" sort="Kelly, Lindsey M" uniqKey="Kelly L" first="Lindsey M." last="Kelly">Lindsey M. Kelly</name>
<name sortKey="Liu, Pengyuan" sort="Liu, Pengyuan" uniqKey="Liu P" first="Pengyuan" last="Liu">Pengyuan Liu</name>
<name sortKey="Luo, Jianhua" sort="Luo, Jianhua" uniqKey="Luo J" first="Jianhua" last="Luo">Jianhua Luo</name>
<name sortKey="Nikiforov, Yuri E" sort="Nikiforov, Yuri E" uniqKey="Nikiforov Y" first="Yuri E." last="Nikiforov">Yuri E. Nikiforov</name>
<name sortKey="Nikiforova, Marina N" sort="Nikiforova, Marina N" uniqKey="Nikiforova M" first="Marina N." last="Nikiforova">Marina N. Nikiforova</name>
<name sortKey="Panebianco, Federica" sort="Panebianco, Federica" uniqKey="Panebianco F" first="Federica" last="Panebianco">Federica Panebianco</name>
<name sortKey="Trivedi, Sumita" sort="Trivedi, Sumita" uniqKey="Trivedi S" first="Sumita" last="Trivedi">Sumita Trivedi</name>
<name sortKey="Yu, Yan P" sort="Yu, Yan P" uniqKey="Yu Y" first="Yan P." last="Yu">Yan P. Yu</name>
</noCountry>
</tree>
</affiliations>
</record>

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Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer

Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer

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Abstract

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