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[Analysis of mutations in the RET proto-oncogene in patients with medullary thyroid tumor].

https://arctichealth.org/en/permalink/ahliterature184294
Source
Genetika. 2003 Jun;39(6):847-54
Publication Type
Article
Date
Jun-2003
Author
F A Amosenko
V Zh Brzhezovskii
L N Liubchenko
M A Shabanov
V M Kozlova
V E Vanushko
T P Kazubskaia
R F Gar'kavtseva
V N Kalinin
Author Affiliation
Research Center for Medical Genetics, Russian Academy of Medical Sciences, Moscow, 115478 Russia. amossenko@medgen.ru
Source
Genetika. 2003 Jun;39(6):847-54
Date
Jun-2003
Language
Russian
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Carcinoma, Medullary - genetics
Exons
Female
Humans
Male
Methionine - genetics
Middle Aged
Multiple Endocrine Neoplasia Type 2a - genetics
Multiple Endocrine Neoplasia Type 2b - genetics
Mutation
Pedigree
Pheochromocytoma - genetics
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-ret
Receptor Protein-Tyrosine Kinases - genetics
Russia
Threonine - genetics
Thyroid Gland - pathology - surgery
Thyroid Neoplasms - genetics
Thyroidectomy
Abstract
The spectrum of mutations of the RET protooncogene was analyzed in Russian patients with inherited or sporadic medullary thyroid carcinoma (MTC). Four RET exons (11, 13, 15, and 16) were subjected to molecular analysis, and mutations were revealed and identified in 47.4% (9/19) patients with sporadic MTC. In total, six mutations (including three new ones) were observed. The most common mutation affected codon 918 to cause substitution of methionine with threonine and accounted for 31.6% alleles. Analysis of exons 11 and 16 revealed four mutations in patients with inherited multiple endocrine neoplasia type 2 (MEN 2). Mutations were found in each patient. Thyroidectomy was performed in four asymptomatic carriers of RET mutations from three MET 2A families (in two families, affected relatives had bilateral pheochromocytoma). In two patients, analysis of the surgery material revealed MTC microfoci in both lobes of the thyroid gland. The results provide the ground for constructing a bank of genetic information on Russian MTC patients with the clinically verified diagnosis.
PubMed ID
12884527 View in PubMed
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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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Cellular DNA pattern, S-phase frequency and survival in papillary thyroid cancer.

https://arctichealth.org/en/permalink/ahliterature25975
Source
Acta Oncol. 1988;27(4):329-33
Publication Type
Article
Date
1988
Author
J. Hrafnkelsson
O. Stål
S. Eneström
J G Jonasson
J. Björnsson
K. Olafsdottir
B. Nordenskjöld
Author Affiliation
Department of Oncology, Regional Hospital, Linköping, Sweden.
Source
Acta Oncol. 1988;27(4):329-33
Date
1988
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aneuploidy
DNA - analysis
Female
Flow Cytometry
Humans
Interphase
Male
Middle Aged
Research Support, Non-U.S. Gov't
Statistics
Thyroid Neoplasms - genetics - mortality
Abstract
A series of 150 patients with papillary thyroid cancer diagnosed in Iceland during the 30-year period from 1955 through 1984 was retrospectively analyzed. Flow cytometric analysis of archival paraffin-embedded material was used to study the prognostic significance of cellular DNA content and s-phase frequency. DNA-aneuploidy was found in 12% of the tumors. It was significantly more common in the elderly, in moderately and poorly differentiated carcinomas, in males and in tumors with a high proportion of s-phase cells. Multivariate analysis using stepwise Cox's model showed aneuploidy, age at diagnosis, lymph node metastasis and tumor extension beyond the thyroid capsule as independent prognostic factors. The frequency of cells in s-phase was generally low (mean 2.7%). Patients with high s-phase frequency (greater than 2.5%) had less favorable prognosis than patients with low values (less than or equal to 2.5%).
PubMed ID
3202993 View in PubMed
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Chromosome aberrations in lymphocytes and clastogenic factors in plasma detected in Belarus children 10 years after Chernobyl accident.

https://arctichealth.org/en/permalink/ahliterature20637
Source
Mutat Res. 1999 Dec 13;446(2):245-53
Publication Type
Article
Date
Dec-13-1999
Author
F. Gemignani
M. Ballardin
F. Maggiani
A M Rossi
A. Antonelli
R. Barale
Author Affiliation
Dipartimento di Scienze dell'Uomo e dell'Ambiente Università di Pisa, Italy.
Source
Mutat Res. 1999 Dec 13;446(2):245-53
Date
Dec-13-1999
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adolescent
Byelarus
Child
Child, Preschool
Chromosome Aberrations
Female
Humans
Lymphocytes - physiology
Male
Mutagens - analysis - metabolism
Plasma - metabolism
Power Plants
Thyroid Neoplasms - genetics
Ukraine
Abstract
In 1996, 10 years after Chernobyl accident, a cytogenetic analysis was carried out to assess whether chromosome aberrant cells (CA) were still detectable in the lymphocytes and clastogenic factors (CFs) were present in the plasma of children coming from Gomel (Belarus), one of the most heavily contaminated regions. Furthermore, the possible contribution of plasmatic CFs to the amount of CA was investigated. The presence of CA was examined in the lymphocytes from 29 thyroid tumour-affected children and 41 healthy children (local controls). Thirty healthy children living in Pisa (Italy) were enrolled in the study as additional controls from an uncontaminated area. No significant difference was observed between the two control groups, whereas a significantly increased frequency of CA was found in the tumour-affected children, as compared with Gomel and Pisa controls (chi 2-test, p 4 Ci/km2) resulted significantly higher than that in other children, either affected or not (p = 0.003). The presence of CFs was analyzed on the plasma ultrafiltrate from 41 children. 7/10 (70%) plasma samples from tumour-affected children and 17/23 (74%) Gomel controls resulted to possess clastogenic activity irrespective of soil contamination levels. No activity was detected in the plasma of eight Pisa controls (0%). The difference between both Gomel groups and Pisa controls was highly significant (p = 0.002). A borderline, but not statistically significant correlation (p = 0.08) was observed between basal CA frequency and CF potency, which became significant (p = 0.03) when only chromosome type of aberrations was considered. We conclude that, although the presence of CFs in the plasma of these children might be partly responsible of the cytogenetic effects observed, the main source of damage has considered to be do to the previous and/or continuous exposure to environmental radiocontaminants. Tumour-affected children may represent a subset of the population either more sensitive to clastogenic damage or exposed to higher levels of contaminants.
PubMed ID
10635348 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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Comet assay on children's leukocytes 8 years after the Chernobyl disaster.

https://arctichealth.org/en/permalink/ahliterature21497
Source
Mutat Res. 1998 Jul 8;415(1-2):151-8
Publication Type
Article
Date
Jul-8-1998
Author
G. Frenzilli
A. Lori
G. Panasiuk
M. Ferdeghini
R. Barale
Author Affiliation
Dipartimento di Scienze dell'Uomo e dell'Ambiente, Università di Pisa, Italy.
Source
Mutat Res. 1998 Jul 8;415(1-2):151-8
Date
Jul-8-1998
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adolescent
Biological Assay
Bleomycin - administration & dosage
Child
DNA Damage
Disasters
Female
Humans
Leukocytes - radiation effects
Male
Power Plants
Thyroid Neoplasms - genetics
Ukraine
Abstract
DNA damage, mainly single strand breaks, was evaluated by single cell gel electrophoresis, in leukocytes of 36 healthy and 14 thyroid cancer-affected children prior to radio-therapy. The children come from the Gomel region, one of the areas most heavily radio-contaminated by the Chernobyl fallout. In addition, leukocytes were treated with a challenge dose of bleomycin (BLM, 1.5 micrograms/ml), to assess the presence of an adaptive response (AR) potentially resulting from chronic exposure to radionuclides. As controls, 13 children living in Pisa (Italy) were enrolled in the study. Children with thyroid cancer show higher (p
PubMed ID
9711271 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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Concordant and discordant familial cancer: Familial risks, proportions and population impact.

https://arctichealth.org/en/permalink/ahliterature282246
Source
Int J Cancer. 2017 Apr 01;140(7):1510-1516
Publication Type
Article
Date
Apr-01-2017
Author
Christoph Frank
Jan Sundquist
Hongyao Yu
Akseli Hemminki
Kari Hemminki
Source
Int J Cancer. 2017 Apr 01;140(7):1510-1516
Date
Apr-01-2017
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Databases, Factual
Family Health
Female
Genetic Predisposition to Disease
Humans
Kidney Neoplasms - genetics
Lung Neoplasms - genetics
Male
Middle Aged
Neoplasms - diagnosis - epidemiology - genetics
Nervous System Neoplasms - genetics
Pancreatic Neoplasms - genetics
Registries
Risk factors
Sweden
Thyroid Neoplasms - genetics
Abstract
Relatives of cancer patients are at an increased risk of the same (concordant) cancer but whether they are at a risk for different (discordant) cancers is largely unknown - beyond well characterized hereditary cancer syndromes - but would be of major scientific and clinical interest. We therefore decided to resolve the issue by analyzing familial risks when family members were diagnosed with any discordant cancers. We compared the population impact of concordant to discordant familial cancer. The Swedish Family-Cancer Database (FCD) was used to calculate familial relative risks (RRs) for family members of cancer patients, for the 27 most common cancers. Population attributable fractions (PAFs) were estimated for concordant and discordant family histories. Discordant cancers in the family were detected as significant risk factors for the majority of cancers, although the corresponding RRs were modest compared to RRs for concordant cancers. Risks increased with the number of affected family members with the highest RRs for pancreatic (2.31), lung (1.69), kidney (1.98), nervous system (1.79) and thyroid cancers (3.28), when 5 or more family members were diagnosed with discordant cancers. For most cancers, the PAF for discordant family history exceeded that for concordant family history. Our findings suggest that there is an unspecific genetic predisposition to cancer with clinical consequences. We consider it unlikely that shared environmental risk factors could essentially contribute to the risks for diverse discordant cancers, which are likely driven by genetic predisposition. The identification of genes that moderately increase the risk for many cancers will be a challenge.
PubMed ID
28006863 View in PubMed
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51 records – page 1 of 6.