Abstract:
:Thyroid cancer is a common endocrine malignancy that encompasses well-differentiated as well as dedifferentiated cancer types. The latter tumors have high mortality and lack effective therapies. Using a paired-end RNA-sequencing approach, we report the discovery of rearrangements involving the anaplastic lymphoma kinase (ALK) gene in thyroid cancer. The most common of these involves a fusion between ALK and the striatin (STRN) gene, which is the result of a complex rearrangement involving the short arm of chromosome 2. STRN-ALK leads to constitutive activation of ALK kinase via dimerization mediated by the coiled-coil domain of STRN and to a kinase-dependent, thyroid-stimulating hormone-independent proliferation of thyroid cells. Moreover, expression of STRN-ALK transforms cells in vitro and induces tumor formation in nude mice. The kinase activity of STRN-ALK and the ALK-induced cell growth can be blocked by the ALK inhibitors crizotinib and TAE684. In addition to well-differentiated papillary cancer, STRN-ALK was found with a higher prevalence in poorly differentiated and anaplastic thyroid cancers, and it did not overlap with other known driver mutations in these tumors. Our data demonstrate that STRN-ALK fusion occurs in a subset of patients with highly aggressive types of thyroid cancer and provide initial evidence suggesting that it may represent a therapeutic target for these patients.
journal_name
Proc Natl Acad Sci U S Aauthors
Kelly LM,Barila G,Liu P,Evdokimova VN,Trivedi S,Panebianco F,Gandhi M,Carty SE,Hodak SP,Luo J,Dacic S,Yu YP,Nikiforova MN,Ferris RL,Altschuler DL,Nikiforov YEdoi
10.1073/pnas.1321937111subject
Has Abstractpub_date
2014-03-18 00:00:00pages
4233-8issue
11eissn
0027-8424issn
1091-6490pii
1321937111journal_volume
111pub_type
杂志文章abstract::The first step in poliovirus replication is binding of virus to a cellular receptor. Mouse L cells, which are resistant to poliovirus infection because they do not bear a poliovirus receptor, were transformed with HeLa cell (human) DNA to poliovirus sensitivity at a frequency of approximately 1 in 50,000 transformants...
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abstract::TREK channels produce background currents that regulate cell excitability. These channels are sensitive to a wide variety of stimuli including polyunsaturated fatty acids (PUFAs), phospholipids, mechanical stretch, and intracellular acidification. They are inhibited by neurotransmitters, hormones, and pharmacological ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.0804172105
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更新日期:2012-03-27 00:00:00
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更新日期:2013-10-08 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2014-12-30 00:00:00
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更新日期:2020-02-11 00:00:00
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更新日期:2017-11-21 00:00:00
abstract::The antigenic sites of horse and rat cytochromes c in the major antigenic region were compared using a panel of variant cytochromes c and a large number of BALB/c mouse monoclonal antibodies (mAbs) in competitive ELISAs. The major antigenic region of cytochrome c is located on the surface opposite of that containing t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1991-05-15 00:00:00
abstract::The brain contains an astonishing diversity of neurons, each expressing only one set of ion channels out of the billions of potential channel combinations. Simple organizing principles are required for us to make sense of this abundance of possibilities and wealth of related data. We suggest that energy minimization s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2010-07-06 00:00:00
abstract::Components in cerebrospinal fluid that are antigenically related to myelin basic protein have been identified by a technique described recently [Barbarese, E., Braun, P. E. & Carson, J. H. (1977) Proc. Natl. Acad. Sci. USA 74, 3360-3364] involving separating the cerebrospinal fluid proteins by sodium dodecyl sulfate/p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1978-04-01 00:00:00
abstract::The structure of the proline-specific aminopeptidase (EC 3.4.11.9) from Escherichia coli has been solved and refined for crystals of the native enzyme at a 2.0-A resolution, for a dipeptide-inhibited complex at 2.3-A resolution, and for a low-pH inactive form at 2.7-A resolution. The protein crystallizes as a tetramer...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.7.3472
更新日期:1998-03-31 00:00:00
abstract::Adeno-associated virus (AAV)-mediated gene therapy is currently being pursued as a treatment for the monogenic disorder α-1-antitrypsin (AAT) deficiency. Results from phase I and II studies have shown relatively stable and dose-dependent increases in transgene-derived wild-type AAT after local intramuscular vector adm...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,多中心研究
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更新日期:2017-02-14 00:00:00
abstract::Studies to elucidate the mode of action of aldosterone have been carried out in the amphibian urinary bladder. The following previously reported hypotheses were evaluated: (1) aldosterone stimulates sodium transport by increasing the amount of sodium available to the sodium pump; (2) aldosterone enhances energy produc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.64.1.330
更新日期:1969-09-01 00:00:00