Rearrangements of TRK proto-oncogene in papillary thyroid carcinomas

Pierotti, Marco A.; Bongarzone, Italia; Borrello, M. G.; Mariani, Cristina; Miranda, Claudia; Sozzi, Gabriella; Greco, Angela

doi:10.1007/bf03349721

Cited by 57 publications

(33 citation statements)

References 10 publications

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“…There is a list of candidate genes with implicated roles in thyroid tumor formation, including ret/ptc, trk, and ras oncogenes, activating mutations of BRAF, the tumor suppressor gene p53, Pax8/peroxisome proliferatoractivated receptor ␦ rearrangement, and candidate tumor suppressor genes on chromosomes 11q13, 3p, and 7q (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). However, there remain thyroid carcinomas for which none of the currently identified genes or mutations can be identified.…”

Section: Introductionmentioning

confidence: 99%

TC-1 Is a Novel Tumorigenic and Natively Disordered Protein Associated with Thyroid Cancer

Sunde

McGrath²,

Young³

et al. 2004

Cancer Research

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A novel gene, thyroid cancer 1 (TC-1), was found recently to be overexpressed in thyroid cancer. TC-1 shows no homology to any of the known thyroid cancer-associated genes. We have produced stable transformants of normal thyroid cells that express the TC-1 gene, and these cells show increased proliferation rates and anchorage-independent growth in soft agar. Apoptosis rates also are decreased in the transformed cells. We also have expressed recombinant TC-1 protein and have undertaken a structural and functional characterization of the protein. The protein is monomeric and predominantly unstructured under conditions of physiologic salt and pH. This places it in the category of natively disordered proteins, a rapidly expanding group of proteins, many members of which play critical roles in cell regulation processes. We show that the protein can be phosphorylated by cyclic AMP-dependent protein kinase and protein kinase C, and the activity of both of these kinases is up-regulated when cells are stably transfected with TC-1. These results suggest that overexpression of TC-1 may be important in thyroid carcinogenesis.

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Section: Introductionmentioning

confidence: 99%

TC-1 Is a Novel Tumorigenic and Natively Disordered Protein Associated with Thyroid Cancer

Sunde

McGrath²,

Young³

et al. 2004

Cancer Research

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“…Mutations of the B-RAF gene have been demonstrated in almost 40% of papillary carcinomas (Fukushima et al, 2003). TRK gene rearrangements (Pierotti et al, 1995) and MET gene overexpression are often found in papillary carcinomas (Di Renzo et al, 1992). RAS gene mutations (Suarez et al, 1990) and PAX8-PPAR-g rearrangements (Kroll et al, 2000) are frequently detected in tumours of the follicular type.…”

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confidence: 99%

UbcH10 overexpression may represent a marker of anaplastic thyroid carcinomas

et al. 2005

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The hybridisation of an Affymetrix HG_U95Av2 oligonucleotide array with RNAs extracted from six human thyroid carcinoma cell lines and a normal human thyroid primary cell culture led us to the identification of the UbcH10 gene that was upregulated by 150-fold in all of the carcinoma cell lines in comparison to the primary culture cells of human normal thyroid origin. Immunohistochemical studies performed on paraffin-embedded tissue sections showed abundant UbcH10 levels in thyroid anaplastic carcinoma samples, whereas no detectable UbcH10 expression was observed in normal thyroid tissues, in adenomas and goiters. Papillary and follicular carcinomas were only weakly positive. These results were further confirmed by RT -PCR and Western blot analyses. The block of UbcH10 protein synthesis induced by RNA interference significantly reduced the growth rate of thyroid carcinoma cell lines. Taken together, these results would indicate that UbcH10 overexpression is involved in thyroid cell proliferation, and may represent a marker of thyroid anaplastic carcinomas.

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“…Using a PCR-based genomic walking technique, Lamant et al 28 demonstrated that the gene involved at 1q25 is TPM3, which encodes nonmuscular tropomyosin and was previously known to similarly rearrange with and activate the NTRK1 receptor tyrosine kinase in some papillary thyroid carcinomas (reviewed in Ref. 29).…”

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confidence: 99%

ATIC-ALK: A Novel Variant ALK Gene Fusion in Anaplastic Large Cell Lymphoma Resulting from the Recurrent Cryptic Chromosomal Inversion, inv(2)(p23q35)

Colleoni

Bridge

Garicochea

et al. 2000

The American Journal of Pathology

162

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The subset of CD30-positive anaplastic large cell lymphomas (ALCL) with the NPM-ALK gene fusion arising from the t(2;5)(p23;q35) forms a distinct clinical and prognostic entity. Recently, various cytogenetic, molecular, and protein studies have provided evidence for the existence of several types of variant ALK fusions in up to 20% of ALK؉ ALCL, of which only one, a TPM3-ALK fusion resulting from a t(1;2)(q25;p23), has so far been cloned. A cryptic inv(2)(p23q35) has been described as another recurrent cytogenetic alteration involving ALK and an unidentified fusion partner in some ALCL. In a screen for variant ALK gene fusions, we identified two ALCL that were negative for NPM-ALK by reverse transcriptase-polymerase chain reaction, but were positive for cytoplasmic ALK with both polyclonal and monoclonal antibodies to the ALK tyrosine kinase domain, consistent with ALK deregulation by an alteration other than the t(2;5) Case 1 was a T-lineage nodal and cutaneous ALCL in a 52-year-old woman, and Case 2 was a Tlineage nodal ALCL in a 12-year-old girl. FISH analysis confirmed ALK rearrangement in both cases. An inverse polymerase chain reaction approach was then used to identify the ALK translocation partner in Case 1. We found an in-frame fusion of ALK to ATIC, a gene previously mapped to 2q34-q35. We then confirmed by DNA polymerase chain reaction the localization of ATIC to yeast artificial chromosome ( Anaplastic large cell lymphoma (ALCL) is recognized as a distinct subtype of non-Hodgkin's lymphoma (NHL) in recent lymphoma classifications. This disease constitutes approximately 5% of all NHL but accounts for 30 to 40% of pediatric large cell lymphomas.1 ALCL expresses Ki-1 (CD30), an antigen originally detected on Reed-Sternberg cells of Hodgkin's disease, later shown to be a member of tumor necrosis factor receptor family. 2,3 In its classical or common form, ALCL shows an often bizarre, anaplastic morphology with sinusoidal infiltration of lymph nodes and a pseudocohesive appearance, and T or null phenotype. 4 The status of ALCL as a discrete entity had long been controversial, 5,6 and its recent separation into at least two subsets (see Discussion) stems from cytogenetic and molecular studies of the translocation seen in about 40 to 60% of cases, t(2;5)(p23;q35). [7][8][9] In 1994, the t(2;5) was found to involve a novel gene at 2p23 encoding a tyrosine kinase, ALK (anaplastic lymphoma kinase), and the NPM (nucleophosmin) gene at

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Rearrangements of TRK proto-oncogene in papillary thyroid carcinomas

Cited by 57 publications

References 10 publications

TC-1 Is a Novel Tumorigenic and Natively Disordered Protein Associated with Thyroid Cancer

TC-1 Is a Novel Tumorigenic and Natively Disordered Protein Associated with Thyroid Cancer

UbcH10 overexpression may represent a marker of anaplastic thyroid carcinomas

ATIC-ALK: A Novel Variant ALK Gene Fusion in Anaplastic Large Cell Lymphoma Resulting from the Recurrent Cryptic Chromosomal Inversion, inv(2)(p23q35)

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