Skip header and navigation

Refine By

6 records – page 1 of 1.

Detection of a novel type of RET rearrangement (PTC5) in thyroid carcinomas after Chernobyl and analysis of the involved RET-fused gene RFG5.

https://arctichealth.org/en/permalink/ahliterature21835
Source
Cancer Res. 1998 Jan 15;58(2):198-203
Publication Type
Article
Date
Jan-15-1998
Author
S. Klugbauer
E P Demidchik
E. Lengfelder
H M Rabes
Author Affiliation
Institute of Pathology, Ludwig Maximilians University of Munich, Germany.
Source
Cancer Res. 1998 Jan 15;58(2):198-203
Date
Jan-15-1998
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adult
Amino Acid Sequence
Artificial Gene Fusion
Base Sequence
Blotting, Northern
Carcinoma, Papillary - genetics - metabolism - pathology
Child
DNA Probes - chemistry
DNA, Neoplasm - genetics
Drosophila Proteins
Female
Gene Expression Regulation, Neoplastic - genetics
Gene Rearrangement - radiation effects
Humans
Immunoenzyme Techniques
Male
Molecular Sequence Data
Neoplasm Proteins - genetics
Neoplasms, Radiation-Induced - genetics - metabolism - pathology
Oncogene Proteins, Fusion - genetics - metabolism
Proto-Oncogene Proteins - genetics - metabolism
Proto-Oncogene Proteins c-ret
RNA, Messenger - biosynthesis
Receptor Protein-Tyrosine Kinases - genetics - metabolism
Research Support, Non-U.S. Gov't
Thyroid Neoplasms - genetics - metabolism - pathology
Ukraine
Abstract
A novel type of RET rearrangement, PTC5, was detected in papillary thyroid carcinomas of two patients exposed to radioactive fallout after Chernobyl. Reverse transcription-PCR and rapid amplification of 5'-cDNA ends revealed a fusion of the ret tyrosine kinase (TK) domain with a sequence identical to that described previously as ret-II. Ret-II is a transfection artifact in NIH3T3 cells and has not yet been detected in any human tumor. Overlapping sequences found in the expressed sequence tag databases enabled us to sequence the COOH terminus of the ret-fused gene 5 (RFG5). The combined data made it possible to assemble a full-length rfg5 protein sequence. Computer-assisted analysis of this sequence reveals four putative coiled-coil structures, possibly involved in dimerization, but no membrane-binding sequences. Northern blots show a ubiquitous RFG5 expression in various normal tissues, including the thyroid gland. In addition to the RFG5/RET, we also detected the reciprocal RET/RFG5 transcript in both tumor samples, suggesting that the rearrangement is based on a balanced reciprocal translocation. In agreement with other rearranged TKs, it is concluded that the transforming action of the new fusion protein rfg5/ret in thyroid tumors may be due to an activation of the ret TK by constitutive expression and dimerization potential of the 5'-fused rfg5 protein. Ret immunohistochemistry indicates that the fusion protein is expressed in all cells of PTC5 tumors, suggesting that RFG5/RET rearrangement is an early event in thyroid carcinogenesis.
PubMed ID
9443391 View in PubMed
Less detail

High prevalence of RET rearrangement in thyroid tumors of children from Belarus after the Chernobyl reactor accident.

https://arctichealth.org/en/permalink/ahliterature22965
Source
Oncogene. 1995 Dec 21;11(12):2459-67
Publication Type
Article
Date
Dec-21-1995
Author
S. Klugbauer
E. Lengfelder
E P Demidchik
H M Rabes
Author Affiliation
Institute of Pathology, Ludwig Maximillyians University of Munich, Germany.
Source
Oncogene. 1995 Dec 21;11(12):2459-67
Date
Dec-21-1995
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adult
Base Sequence
Carcinoma, Papillary - genetics
Child
Child, Preschool
Drosophila Proteins
Female
Gene Rearrangement
Humans
Infant
Male
Middle Aged
Molecular Sequence Data
Neoplasms, Radiation-Induced - genetics
Nuclear Reactors
Polymerase Chain Reaction
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-ret
Proto-Oncogenes
Receptor Protein-Tyrosine Kinases - genetics
Research Support, Non-U.S. Gov't
Thyroid Neoplasms - etiology - genetics
Ukraine
Abstract
RET rearrangement was studied in papillary thyroid carcinomas (PTC) of children exposed to radioactive fallout in Belarus after the Chernobyl accident. To detect RET rearrangement in small tissue samples from thyroidectomy specimen (12 PTC of children; 2 PTC and 1 follicular carcinoma of adults; non-tumorous thyroid tissue of 4 children and 4 adults as controls), a RT-multiplex PCR was developed using primers suited to amplify fragments in different quantities depending on the presence or absence of RET rearrangements in the tissues. The type of rearrangement was determined by RT-PCR and direct sequencing using primers for ret/PTC1, 2 and 3. Two-thirds of the papillary thyroid carcinomas of the children revealed a RET rearrangement, with ret/PTC3 being more frequent by a factor of 3 than ret/PTC1. ret/PTC2 was not detected. All RET rearrangement-positive tumors had lymph node metastasis while half of the tumors with wild-type cRET had not. More than half of the cases with ret/PTC3 expressed not only the ELE/RET transcript as expected, but also the RET/ELE transcript. Intrachromosomal rearrangement involving RET and the adjacent H4 or ELE gene on chromosome no. 10 is a very frequent event in thyroid cancer of children of the Chernobyl-contaminated zone of Belarus.
PubMed ID
8545102 View in PubMed
Less detail

Molecular analysis of new subtypes of ELE/RET rearrangements, their reciprocal transcripts and breakpoints in papillary thyroid carcinomas of children after Chernobyl.

https://arctichealth.org/en/permalink/ahliterature21773
Source
Oncogene. 1998 Feb 5;16(5):671-5
Publication Type
Article
Date
Feb-5-1998
Author
S. Klugbauer
E P Demidchik
E. Lengfelder
H M Rabes
Author Affiliation
Institute of Pathology, Ludwig Maximilians University of Munich, Germany.
Source
Oncogene. 1998 Feb 5;16(5):671-5
Date
Feb-5-1998
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Artificial Gene Fusion - radiation effects
Base Sequence
Carcinoma, Papillary - etiology - genetics
Child, Preschool
Chromosome Breakage
DNA Repair
DNA, Neoplasm - radiation effects
Drosophila Proteins
Female
Gene Rearrangement - radiation effects
Genome
Humans
Infant
Molecular Sequence Data
Neoplasms, Radiation-Induced - etiology - genetics
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-ret
RNA, Messenger - genetics - metabolism
Receptor Protein-Tyrosine Kinases - genetics
Research Support, Non-U.S. Gov't
Thyroid Neoplasms - etiology - genetics
Ukraine
Abstract
A high prevalence of RET rearrangements is found in papillary thyroid carcinomas (PTC) of children from Belarus after the Chernobyl reactor accident. The ELE/RET rearrangement (PTC3) is prevailing. Aberrant types of ELE/RET rearrangement have been found with a truncated ELE1 gene: As compared with the common form (PTC3r1) one aberrant type is shorter by one 144 bp exon (PTC3r2) (three cases); in the second atypic form (PTC3r3) the ELE1 part is 18 bp shorter than in PTC3r1. In agreement with the observation that the oncogenic RET is generated by a paracentric inversion at chromosome 10, we found not only ELE/RET, but also RET/ELE transcripts in these tumors. Sequencing of the breakpoint regions at the genomic DNA level revealed DNA modifications that might be relevant for illegitimate recombination after DNA doublestrand breaks. The high prevalence of ELE/RET rearrangements and various subtypes appears to be typical for radiation-induced thyroid carcinomas of children after the Chernobyl reactor accident.
PubMed ID
9482114 View in PubMed
Less detail

A new form of RET rearrangement in thyroid carcinomas of children after the Chernobyl reactor accident.

https://arctichealth.org/en/permalink/ahliterature22485
Source
Oncogene. 1996 Sep 5;13(5):1099-1102
Publication Type
Article
Date
Sep-5-1996
Author
S. Klugbauer
E. Lengfelder
E P Demidchik
H M Rabes
Author Affiliation
Institute of Pathology, Ludwig Maximilians University of Munich, Germany.
Source
Oncogene. 1996 Sep 5;13(5):1099-1102
Date
Sep-5-1996
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Amino Acid Sequence
Base Sequence
Carcinoma - genetics
Child
Drosophila Proteins
Gene Rearrangement
Humans
Molecular Sequence Data
Neoplasms, Radiation-Induced - genetics
Power Plants
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-ret
Receptor Protein-Tyrosine Kinases - genetics
Research Support, Non-U.S. Gov't
Sequence Analysis, DNA
Thyroid Neoplasms - genetics
Ukraine
Abstract
Intrachromosomal rearrangements involving the RET and the adjacent H4 or ELE1 gene are very frequent events in thyroid cancer of children from Belarus after the Chernobyl reactor accident (Klugbauer et al., 1995). The fusion product between ELE1 and RET (RET/ PTC3) seems to be the prevailing type of rearrangement as shown in a recently published study using a novel RT multiplex PCR approach in combination with the identification of the rearrangement type by RT-PCR and direct sequencing. Now we found a new type of RET rearrangement: By the 5'RACE method we demonstrated in cDNA the fusion of the tyrosine kinase domain of RET with a truncated ELE1 gene shorter than the ELE1 in RET/PTC3. Sequencing of genomic DNA revealed a rearrangement breakpoint at position 41 of a new ELE1 intron (522 bp in length). The new oncogene RET/ delta PTC3 is shortened by one ELE1 exon of 144 bp in length. Structural considerations of the ele1 amino terminal of RET/ delta PTC3 suggest that the transforming activity of the fusion protein is apparently not affected by this truncation. The exon lacking in RET/ delta PTC3 was found to code in the reciprocal transcript RET/ delta ELE1 and increased its size by 144 bp. Obviously the new and possibly additional ELE/RET fusion molecules might even increase the high prevalence of ELE1/RET rearrangements in thyroid carcinomas of children after the Chernobyl reactor accident.
PubMed ID
8806700 View in PubMed
Less detail

A novel type of RET rearrangement (PTC8) in childhood papillary thyroid carcinomas and characterization of the involved gene (RFG8).

https://arctichealth.org/en/permalink/ahliterature20059
Source
Cancer Res. 2000 Dec 15;60(24):7028-32
Publication Type
Article
Date
Dec-15-2000
Author
S. Klugbauer
A. Jauch
E. Lengfelder
E. Demidchik
H M Rabes
Author Affiliation
Institute of Pathology, Ludwig Maximilians University of Munich, Germany.
Source
Cancer Res. 2000 Dec 15;60(24):7028-32
Date
Dec-15-2000
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adolescent
Amino Acid Sequence
Base Sequence
Blotting, Northern
Carcinoma, Papillary - genetics
Chromosomes, Human, Pair 18
Cytoplasm - metabolism
DNA, Complementary - metabolism
Drosophila Proteins
Female
Gene Rearrangement
Humans
In Situ Hybridization, Fluorescence
Male
Molecular Sequence Data
Power Plants
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-ret
RNA, Messenger - metabolism
Receptor Protein-Tyrosine Kinases - genetics
Research Support, Non-U.S. Gov't
Reverse Transcriptase Polymerase Chain Reaction
Thyroid Neoplasms - genetics
Tissue Distribution
Translocation, Genetic
Ukraine
Abstract
As part of ongoing studies on the RET rearrangement frequency in children with papillary thyroid carcinoma (PTC) after their exposure to radioactive iodine after the Chernobyl reactor accident, new methods for the detection of novel types of RET rearrangements are being developed. In this study, an improved reverse transcription-PCR strategy is used successfully to identify a new type of RET rearrangement. This rearrangement is designated PTC8 and the involved RET-fused gene (RFG) as RFG8. The identification of two reciprocal transcripts coding for the RFG8/RET and RET/RFG8 fusions suggests that the PTC8 rearrangement results from a balanced chromosomal translocation. With a view to clarify its role in tumor induction, we compared the fusion products with those of previously described RET rearrangements. We therefore sequenced and characterized the RFG8 cDNA, which showed no significant similarity to any functional protein described as yet. RFG8 is located on chromosome 18q21-22 and is expressed ubiquitously. Bioinformatic analysis predicts with a high probability that the corresponding rfg8 protein is located in the cytoplasm and is involved putatively in intracellular transport processes. Furthermore, we identified coiled-coil structures upstream of the breakpoint with one of the coiled-coils showing dimerization capability. Thus the rfg8/ret fusion protein exhibits structures for oncogenic activation that are similar to those observed in previously described RET fusions.
PubMed ID
11156407 View in PubMed
Less detail

Translocation t(10;14)(q11.2:q22.1) fusing the kinetin to the RET gene creates a novel rearranged form (PTC8) of the RET proto-oncogene in radiation-induced childhood papillary thyroid carcinoma.

https://arctichealth.org/en/permalink/ahliterature20405
Source
Cancer Res. 2000 Jun 1;60(11):2786-9
Publication Type
Article
Date
Jun-1-2000
Author
K. Salassidis
J. Bruch
H. Zitzelsberger
E. Lengfelder
A M Kellerer
M. Bauchinger
Author Affiliation
Institute of Radiation Biology, Ludwig Maximilians University, München, Germany.
Source
Cancer Res. 2000 Jun 1;60(11):2786-9
Date
Jun-1-2000
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Base Sequence
Carcinoma, Papillary - etiology - genetics
Cells, Cultured
Chromosomes, Artificial, Yeast
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 14
DNA Mutational Analysis
Drosophila Proteins
Humans
In Situ Hybridization, Fluorescence
Membrane Proteins
Molecular Sequence Data
Neoplasms, Radiation-Induced - genetics
Power Plants
Protein-Tyrosine Kinase - genetics
Proto-Oncogene Proteins - genetics - metabolism
Proto-Oncogene Proteins c-ret
RNA, Messenger - metabolism
Receptor Protein-Tyrosine Kinases - genetics - metabolism
Receptors, Cell Surface - genetics - metabolism
Research Support, Non-U.S. Gov't
Reverse Transcriptase Polymerase Chain Reaction
Thyroid Gland - radiation effects
Thyroid Neoplasms - etiology - genetics
Translocation, Genetic
Ukraine
Abstract
Evaluation of 20 cases of radiation-induced childhood papillary thyroid carcinoma using fluorescence in situ hybridization demonstrated the presence of clonal translocations affecting the RET locus. Semiquantitative reverse transcription-PCR indicated overexpression of the RET tyrosine kinase (TK) domain in four cases. In two cases, the RET rearrangements PTC6 and PTC7 were identified and assigned to balanced translocations t(7;10)(q32;q11.2) and t(1;10)(p13;q11.2), respectively. In one case with a balanced translocation t(10;14)(q11.2;q22.1), 5' rapid amplification of cDNA ends revealed a novel type of RET oncogenic activation (PTC8), arising from a fusion of the 5' part of the kinectin (KTN1) gene to the TK domain of the RET gene. The presence of coiled-coil domains in the resulting ktn1/ret fusion protein suggests ligand-independent dimerization and thus constitutive activation of the ret TK domain.
PubMed ID
10850414 View in PubMed
Less detail

6 records – page 1 of 1.