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31 records – page 1 of 4.

BRAF mutations are not a major event in post-Chernobyl childhood thyroid carcinomas.

https://arctichealth.org/en/permalink/ahliterature17515
Source
J Clin Endocrinol Metab. 2004 Sep;89(9):4267-71
Publication Type
Article
Date
Sep-2004
Author
Jorge Lima
Vítor Trovisco
Paula Soares
Valdemar Máximo
João Magalhães
Giuliana Salvatore
Massimo Santoro
Tatyana Bogdanova
Mykola Tronko
Alexander Abrosimov
Steve Jeremiah
Gerry Thomas
Dillwyn Williams
Manuel Sobrinho-Simões
Author Affiliation
Institute of Molecular Pathology and Immunology, University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal.
Source
J Clin Endocrinol Metab. 2004 Sep;89(9):4267-71
Date
Sep-2004
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Carcinoma, Papillary - genetics
Child
Female
Gene Rearrangement
Humans
Male
Mutation
Neoplasms, Radiation-Induced - genetics
Oncogene Proteins - genetics
Power Plants
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins c-raf - genetics
Proto-Oncogene Proteins c-ret
Receptor Protein-Tyrosine Kinases - genetics
Research Support, Non-U.S. Gov't
Thyroid Neoplasms - genetics
Ukraine
Abstract
The BRAF gene has been shown to be a major target for mutations in papillary thyroid carcinoma (PTC) (36-69%), which forms almost all of the over 2000 cases of thyroid carcinoma that have occurred in Chernobyl. BRAF is activated by point mutation, and were it to occur at a high frequency in Chernobyl-related tumors, it would challenge the dominant role of double-strand breaks in radiation-induced PTC. In a previous study, we detected the BRAF V600E mutation in 46% (23 of 50) of sporadic adult PTC. Using the same methodology, we have analyzed 34 post-Chernobyl PTC and detected RET/PTC rearrangements in 14 (41%) and BRAF mutations (V600E) in four (12%). These two alterations did not coexist in any PTCs. The mean age at exposure of patients with PTC showing BRAF mutation was higher than that of patients with tumors without BRAF mutation irrespective of their RET status. We have also analyzed 17 sporadic cases of childhood PTC and found that only one (6%) harbored the BRAF V600E mutation. We conclude that the frequency of BRAF mutations is significantly lower (P = 0.0008) in post-Chernobyl PTC than in adult sporadic PTC, whereas no significant difference was found between post-Chernobyl and sporadic childhood PTCs.
Notes
Comment In: J Clin Endocrinol Metab. 2004 Sep;89(9):4264-615356019
PubMed ID
15356020 View in PubMed
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BRAF mutations in an Italian cohort of thyroid cancers.

https://arctichealth.org/en/permalink/ahliterature17594
Source
Clin Endocrinol (Oxf). 2004 Aug;61(2):239-43
Publication Type
Article
Date
Aug-2004
Author
Laura Fugazzola
Deborah Mannavola
Valentina Cirello
Guia Vannucchi
Marina Muzza
Leonardo Vicentini
Paolo Beck-Peccoz
Author Affiliation
Institute of Endocrine Sciences, University of Milan, Milan, Italy. laurafugazzola@hotmail.com
Source
Clin Endocrinol (Oxf). 2004 Aug;61(2):239-43
Date
Aug-2004
Language
English
Publication Type
Article
Keywords
Adult
Carcinoma, Papillary - genetics - pathology
Carcinoma, Papillary, Follicular - genetics
Cell Transformation, Neoplastic - genetics
Cohort Studies
DNA Mutational Analysis - methods
DNA, Neoplasm - genetics
Exons - genetics
Female
Heterozygote
Humans
Male
Middle Aged
Mutation
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins c-raf - genetics
Thyroid Neoplasms - genetics - pathology
Abstract
OBJECTIVE: Recently, a somatic point mutation of the BRAF gene (V599E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC) with a variable frequency (about 25-70%) in different series from USA, Japan, Portugal and Ukraine. DESIGN: In the present study, the genetic analysis of BRAF in an Italian cohort of 65 thyroid tumours with corresponding normal tissues and 21 thyroid benign disorders is reported. METHODS: For BRAF analysis, the somatic DNA was PCR amplified by means of specific intronic primers and PCR products were directly sequenced. Statistical analyses were obtained by means of Fisher's exact test. RESULTS: All mutations detected involved a T > A transversion at 1796 (V599E) and were heterozygous. Overall, BRAF(V599E) mutation was found in 18/56 (32.1%) PTCs. According to the histological type of the tumour, the mutation was present in 38.3% of cases of conventional PTC (18/47), in 0/6 follicular variant of PTC, in 0/3 oncocytic variant of PTC. No BRAF mutations were detected either in five follicular carcinomas, or in four poorly differentiated or undifferentiated cancers or in benign thyroid disorders. No statistically significant correlation of BRAF mutation with patient age and gender, with multicentricity of the tumour, with the lymphocytic infiltration of the tissue, with the stage and with the recurrence rate, was found. BRAF(V599E) tended to be associated, although not significantly, with a greater volume and extension of the tumour and with lymph-nodal metastases at surgery. CONCLUSIONS: In conclusion, the present study on the first Italian series of thyroid cancers shows a frequency of 38.3% of BRAF(V599E) in the classical variant of PTC, confirming the key role of this mutation in promoting tumourigenesis.
PubMed ID
15272920 View in PubMed
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[CD44 gene expression in cancerous thyroid cells]

https://arctichealth.org/en/permalink/ahliterature20866
Source
Tsitol Genet. 1999 Mar-Apr;33(2):27-32
Publication Type
Article
Author
A V Pisarchik
N A Kartel'
G Z Ermak
J. Figge
Source
Tsitol Genet. 1999 Mar-Apr;33(2):27-32
Language
Russian
Publication Type
Article
Keywords
Accidents, Radiation
Alternative Splicing - genetics - radiation effects
Antigens, CD44 - genetics - radiation effects
Base Sequence
Byelarus
Carcinoma, Papillary - genetics
Child
Comparative Study
DNA Primers
English Abstract
Gene Expression Regulation, Neoplastic - genetics - radiation effects
Humans
Molecular Sequence Data
Oncogenes - genetics - radiation effects
Polymerase Chain Reaction - methods
Power Plants
RNA, Messenger - genetics - radiation effects
Thyroid Gland - radiation effects
Thyroid Neoplasms - genetics
Ukraine
Abstract
The peculiarities of alternative CD44 mRNA splicing in thyroid cancer tissue of children from radiocontaminated areas was investigated. CD44 gene expression in thyroid cancer tissues of children exposed to radiation resembled that in spontaneously emerged cancers. It was concluded that CD44 gene expression is not the primary target of radioactive irradiation. Probably, the CD44 mRNA splicing deregulation is the consequence of cancer.
PubMed ID
10465838 View in PubMed
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Challenging dogma in thyroid cancer molecular genetics--role of RET/PTC and BRAF in tumor initiation.

https://arctichealth.org/en/permalink/ahliterature17516
Source
J Clin Endocrinol Metab. 2004 Sep;89(9):4264-6
Publication Type
Article
Date
Sep-2004
Author
James A Fagin
Source
J Clin Endocrinol Metab. 2004 Sep;89(9):4264-6
Date
Sep-2004
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Carcinoma, Papillary - genetics
Child
Gene Rearrangement
Humans
Mutation
Neoplasms, Radiation-Induced - genetics
Oncogene Proteins - genetics
Power Plants
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins c-raf - genetics
Proto-Oncogene Proteins c-ret
Receptor Protein-Tyrosine Kinases - genetics
Research Support, U.S. Gov't, P.H.S.
Thyroid Neoplasms - etiology - genetics
Ukraine
Notes
Comment On: J Clin Endocrinol Metab. 2004 Sep;89(9):4267-7115356020
Comment On: J Clin Endocrinol Metab. 2004 Sep;89(9):4272-915356021
Comment On: J Clin Endocrinol Metab. 2004 Sep;89(9):4280-415356022
PubMed ID
15356019 View in PubMed
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Chromosome translocations in thyroid tissues from Belarussian children exposed to radioiodine from the Chernobyl accident, measured by FISH-painting.

https://arctichealth.org/en/permalink/ahliterature22424
Source
Int J Radiat Biol. 1996 Nov;70(5):513-6
Publication Type
Article
Date
Nov-1996
Author
L. Lehmann
H. Zitzelsberger
A M Kellerer
H. Braselmann
U. Kulka
V. Georgiadou-Schumacher
T. Negele
F. Spelsberg
E. Demidchik
E. Lengfelder
M. Bauchinger
Author Affiliation
GSF-Institute für Strahlenbiologie, Oberschleissheim, Germany.
Source
Int J Radiat Biol. 1996 Nov;70(5):513-6
Date
Nov-1996
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adolescent
Carcinoma, Papillary - genetics
Cells, Cultured
Child
Child, Preschool
Chromosomes, Human, Pair 1
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 4
Female
Humans
In Situ Hybridization, Fluorescence
Infant
Infant, Newborn
Iodine Radioisotopes
Male
Neoplasms, Radiation-Induced - genetics
Power Plants
Thyroid Gland - radiation effects
Thyroid Neoplasms - genetics
Translocation, Genetic
Ukraine
Abstract
Chromosome painting of chromosomes 1, 4 and 12 was performed on metaphase preparations of cultured thyroid cells to analyse the frequency of radiation-induced stable chromosome translocations in papillary thyroid carcinomas from 40 Belarussian children exposed to radioiodine from the Chernobyl accident, and from 31 reference case. As expected, we found the highest translocation frequencies in secondary thyroid tumours after radiotherapy, but there were also high frequencies in tumour tissues as well as in non-tumourous tissues from childhood papillary carcinoma samples from Belarus. Among the Belarussian tumours the cases from the Gomel region exhibited the highest frequency of translocations and five cases lie within the range of frequencies observed in secondary thyroid tumours after radiotherapy. The findings support the assumption that radiation was the principal cause of the tumours in Belarus, but they indicate also that only a minority of the Belarus cases, which have developed papillary carcinomas, were exposed to very high doses of radioiodine.
PubMed ID
8947531 View in PubMed
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Comparison of the breakpoint regions of ELE1 and RET genes involved in the generation of RET/PTC3 oncogene in sporadic and in radiation-associated papillary thyroid carcinomas.

https://arctichealth.org/en/permalink/ahliterature22057
Source
Genomics. 1997 Jun 1;42(2):252-9
Publication Type
Article
Date
Jun-1-1997
Author
I. Bongarzone
M G Butti
L. Fugazzola
F. Pacini
A. Pinchera
T V Vorontsova
E P Demidchik
M A Pierotti
Author Affiliation
Division of Experimental Oncology A, Istituto Nazionale Tumori, Milan, Italy.
Source
Genomics. 1997 Jun 1;42(2):252-9
Date
Jun-1-1997
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Base Sequence
Carcinoma, Papillary - genetics
Cloning, Molecular
Comparative Study
DNA Primers - genetics
DNA, Neoplasm - genetics
Exons
Gene Rearrangement - radiation effects
Humans
Introns
Molecular Sequence Data
Neoplasms, Radiation-Induced - genetics
Oncogenes - radiation effects
Polymerase Chain Reaction
Recombination, Genetic - radiation effects
Research Support, Non-U.S. Gov't
Thyroid Neoplasms - genetics
Ukraine
Abstract
The RET/PTC3 oncogene is an activated form of the RET protooncogene, which is frequently rearranged in papillary thyroid carcinoma. RET/PTC3 results from a structural rearrangement between the ELE1 and the RET genes, and it has been observed in both sporadic and radiation-associated post-Chernobyl tumors. To understand the molecular basis that predisposes RET and ELE1 genes to be recurrent targets of "illegitimate" recombination, we examined the genomic regions containing the ELE1/RET breakpoints of six sporadic and three post-Chernobyl tumors in two papillary carcinomas of different origins. Our data indicated, in both genes, a clustering of the breakpoints in regions designated ELE1-bcr (1.8 kb) and RET-bcr (1.9 kb). Notably, in all sporadic tumors and in one post-Chernobyl tumor the ELE1/RET recombination corresponded with short sequences of homology (3-7 nt) between the two rearranging genes. In addition, we observed an interesting distribution of the post-Chernobyl breakpoints in ELE1-bcr located within an Alu element, or in between two close Alu elements, and always in A+T-rich regions.
PubMed ID
9192845 View in PubMed
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Copy number and gene expression alterations in radiation-induced papillary thyroid carcinoma from chernobyl pediatric patients.

https://arctichealth.org/en/permalink/ahliterature98915
Source
Thyroid. 2010 May;20(5):475-87
Publication Type
Article
Date
May-2010
Author
Leighton Stein
Jenniffer Rothschild
Jesse Luce
John K Cowell
Geraldine Thomas
Tatania I Bogdanova
Mycola D Tronko
Lesleyann Hawthorn
Author Affiliation
Roswell Park Cancer Institute , Department of Cancer Genetics, Buffalo, New York, USA.
Source
Thyroid. 2010 May;20(5):475-87
Date
May-2010
Language
English
Publication Type
Article
Keywords
Carcinoma, Papillary - genetics - pathology
Chernobyl Nuclear Accident
Child
DNA - genetics
Female
Gene Deletion
Gene Dosage
Gene Expression Regulation, Neoplastic
Heterozygote
Humans
Loss of Heterozygosity
Male
Neoplasms, Radiation-Induced - genetics - pathology
Polymorphism, Single Nucleotide - genetics
Principal Component Analysis
RNA - genetics
Thyroid Neoplasms - genetics - pathology
Ukraine - epidemiology
Abstract
BACKGROUND: Following exposure to radiation during the Chernobyl fallout tragedy, papillary thyroid carcinoma (PTC) increased significantly in individuals who were children at the time of the accident. We have used two high-throughput, whole genome platforms to analyze radiation-induced PTCs from pediatric patients from the Chernobyl region. METHODS: We performed comparative genomic hybridization using Affymetrix 50K Mapping arrays and gene expression profiling on 10 pediatric post-Chernobyl PTCs obtained from patients living in the region. We performed an overlay analysis of these two data sets. RESULTS: Many regions of copy number alterations (CNAs) were detected including novel regions that had never been associated with PTCs. Increases in copy numbers were consistently found on chromosomes 1p, 5p, 9q, 12q, 13q, 16p, 21q, and 22q. Deletions were observed less frequently and were mapped to 1q, 6q, 9q, 10q, 13q, 14q, 21q, and 22q. Gene expression analysis revealed that most of the altered genes were also perturbed in sporadic adult PTC; however, 141 gene expression changes were found to be unique to the post-Chernobyl tumors. The genes with the highest increases in expression that were novel to the pediatric post-Chernobyl tumors were TESC, PDZRN4, TRAa/TRDa, GABBR2, and CA12. The genes showing the largest expression decreases included PAPSS2, PDLIM3, BEXI, ANK2, SORBS2, and PPARGCIA. An overlay analysis of the gene expression and CNA profiles was then performed. This analysis identified genes showing both CNAs and concurrent gene expression alterations. Many of these are commonly seen in sporadic PTC such as SERPINA, COL8A, and PDX, while others were unique to the radiation-induced profiles including CAMK2N1, AK1, DHRS3, and PDE9A. CONCLUSIONS: This type of analysis allows an assessment of gene expression changes that are associated with a physical mechanism. These genes and chromosomal regions are potential markers for radiation-induced PTC.
PubMed ID
19725780 View in PubMed
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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
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Different significance of ret/PTC(1) and ret/PTC(3) rearrangements in thyroid carcinogenesis: lesson from two subgroups of patients with papillary thyroid carcinomas showing the highest incidence of ret/PTC activation.

https://arctichealth.org/en/permalink/ahliterature19967
Source
J Clin Endocrinol Metab. 2001 Mar;86(3):1429
Publication Type
Article
Date
Mar-2001
Author
F. Cetta
M. Gori
G. Montalto
M. Zuckermann
P. Toti
Source
J Clin Endocrinol Metab. 2001 Mar;86(3):1429
Date
Mar-2001
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Carcinoma, Papillary - genetics - radiotherapy
Drosophila Proteins
Gene Rearrangement
Humans
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-ret
Receptor Protein-Tyrosine Kinases - genetics
Research Support, Non-U.S. Gov't
Thyroid Neoplasms - etiology - genetics
Ukraine
Notes
Comment On: J Clin Endocrinol Metab. 1997 Jun;82(6):2015-79177425
Comment On: J Clin Endocrinol Metab. 1998 Mar;83(3):1003-69506763
Comment On: J Clin Endocrinol Metab. 1999 Nov;84(11):4232-810566678
Comment On: J Clin Endocrinol Metab. 2000 Jan;85(1):286-9210634400
PubMed ID
11238550 View in PubMed
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Distinct frequency of ret rearrangements in papillary thyroid carcinomas of children and adults from Belarus.

https://arctichealth.org/en/permalink/ahliterature21258
Source
Int J Cancer. 1999 Jan 5;80(1):32-8
Publication Type
Article
Date
Jan-5-1999
Author
J. Smida
K. Salassidis
L. Hieber
H. Zitzelsberger
A M Kellerer
E P Demidchik
T. Negele
F. Spelsberg
E. Lengfelder
M. Werner
M. Bauchinger
Author Affiliation
Radiobiological Institute, University of Munich, Germany.
Source
Int J Cancer. 1999 Jan 5;80(1):32-8
Date
Jan-5-1999
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adenocarcinoma, Follicular - genetics - pathology - surgery
Adolescent
Adult
Age Factors
Aged
Byelarus
Carcinoma, Papillary - genetics - pathology - surgery
Child
Comparative Study
Drosophila Proteins
Female
Gene Rearrangement
Germany
Humans
Male
Middle Aged
Neoplasm Staging
Neoplasms, Radiation-Induced - genetics - pathology - surgery
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-ret
Proto-Oncogenes
RNA, Messenger - analysis
Receptor Protein-Tyrosine Kinases - genetics
Research Support, Non-U.S. Gov't
Thyroid Neoplasms - genetics - pathology - surgery
Ukraine
Abstract
Rearrangements of the ret oncogene were investigated in papillary thyroid carcinomas (PTC) from 51 Belarussian children with a mean age of 3 years at the time of the Chernobyl radiation accident. For comparison, 16 PTC from exposed Belarussian adults and 16 PTC from German patients without radiation history were included in the study. ret rearrangements were detected and specified by RT-PCR and direct sequencing using specific primers for ret/PTC1, 2 and 3. Only ret/PTC1, and no ret/PTC3, was found in the adult patients, with a frequency of 69% for the Belarussian cases, but of only 19% in the German patients. In contrast, 13 ret/PTC3 (25.5%) and 12 ret/PTC1 (23.5%) rearrangements were present in PTC from Belarussian children. Thus, our study reveals about a 1:1 ratio of ret/PTC3 and ret/PTC1, in contrast to earlier studies with lower numbers of cases and exhibiting a high predominance of ret/PTC3 (ratio about 3:1). A ratio (2.5:1) similar to that in earlier investigations (diagnosed 1991-94) was obtained for cases included in our study that were diagnosed in 1993/94. The present data suggest that ret/PTC3 may be typical for radiation-associated childhood PTC with a short latency period, whereas ret/PTC1 may be a marker for later-occurring PTC of radiation-exposed adults and children.
PubMed ID
9935226 View in PubMed
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31 records – page 1 of 4.