Sequence variant in the intron 10 of the RET oncogene in a patient with microfollicular thyroid carcinoma with medullar differentiation - Implications for newly generated chi-like sequence

Autor: Radan Dzodic, Gorana Nesković, Bogomir Dimitrijević, Miroslav Opric, Boban Stanojevic, Emilija Veljkovic, Zorka Milovanovic
Rok vydání: 2004
Předmět:
Cancer Research
endocrine system diseases
DNA Mutational Analysis
Molecular Sequence Data
Biology
Proto-Oncogene Mas
Germline
Thyroid carcinoma
microfollicular thyroid carcinoma
03 medical and health sciences
0302 clinical medicine
Adenocarcinoma
Follicular
Databases
Genetic
Carcinoma
medicine
Humans
Point Mutation
Thyroid Neoplasms
030304 developmental biology
Sequence (medicine)
Oncogene Proteins
Genetics
0303 health sciences
Base Sequence
Proto-Oncogene Proteins c-ret
Thyroid
Intron
Receptor Protein-Tyrosine Kinases
DNA
Neoplasm
Sequence Analysis
DNA
Hematology
General Medicine
Middle Aged
medicine.disease
Phenotype
Introns
3. Good health
Cell Transformation
Neoplastic
medicine.anatomical_structure
Oncology
Tumor progression
030220 oncology & carcinogenesis
Cancer research
RET oncogene
Female
Chi-like intronic sequence variant
Mitogens
Zdroj: Medical Oncology
Popis: Sequence alterations in the RET proto-oncogene are becoming increasingly important to clinical assessment of the malignant disease of the thyroid. A spectrum of mutations is necessary to establish comprehensive phenotype to genotype relationship relevant to diagnosis and therapy of thyroid malignancies. We aimed to append to the increasing database of these oncogenic lesions and, therefore, analyzed DNA from tumor tissue and constitutive DNA from a patient with thyroid carcinoma. Mutational screening and sequence characterization of the RET proto-oncogene was performed to include part of the intronic sequences. We report a germline sequence variant in DNA from the patient diagnosed with microfollicular thyroid carcinoma. The carcinoma presented not as fully developed medullar carcinoma (MTC) but as microfollicular carcinoma with tendency to evolve into MTC. We characterized the sequence variant located in the intron 10 of the RET oncogene as an A to G substitution denoted IVS10 + 4G. The described sequence alteration generates a chi-like sequence surrounded by several chi-like sequences with recombinational potential. Such alteration may be involved in the pathogenesis of the microfollicular carcinoma via genome destabilization through homologous recombination in the process of tumor progression. This result further substantiates the importance of the database correlating specific sequence variations in the RET gene with distinct disease phenotypes.
Databáze: OpenAIRE
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