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

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

Le Grand écho du Nord de la France

04 mai 19021902/05/04 (A84,N124).Appartient à l’ensemble documentaire : NordPdeC

Molecular characterization and phylogenetic analysis of full-genome HBV subgenotype D3 sequences from Serbia

Hepatitis B virus (HBV) is classified into 8 genotypes with distinct geographical distribution. Genotype D (HBV/D) has the widest distribution area and is comprised of 7 subgenotypes. Subgenotypes D1, D2 and D3 appear worldwide, while D4-D7 have a more restricted distribution. Within the Mediterranean area, HBV/D and subgenotype D3 are the most prevalent. The purpose of this study was to characterize the full genome of Serbian HBV/D3 isolates by comparison and phylogenetic analysis with HBV/D3 sequences (66 samples) found in GeneBank/DDBJ databases from different parts of the world. Isolates were obtained from three patients diagnosed with chronic hepatitis B (HBsAg +). All three isolates have two very rare nucleotide substitutions, A929T and T150A, which indicate the same ancestor. Phylogenetic analysis of HBV/D3 genome sequences throughout the world follows an ethno-geographical origin of isolates with rare exceptions, which could be explained by human travelling and migration. The geographically close but ethnically different Serbian and Italian isolates clustered in the same subnode, and on a common branch with strains from Northern Canada. To test the apparently close HBV phylogenetic relationship between completely separated patients from Serbia and Northern Canada we analyzed in depth a 440 bp region of the HBsAg from Canadian (n = 73) and Serbian (n = 70) isolates. The constructed parsimony tree revealed that strains from Serbia and Northern Canada fell along the same branch which indicates independent evolution within regions of each country, Considering that HBsAg sequence has limited variability for phylogenetic analyses, our hypothesis needs further confirmation with more HBV complete genome sequences. (C) 2011 Elsevier B.V. All rights reserved,Ministry of Science and Technological Development of the Republic of Serbia [173003, 173049