[Sulfonium derivatives of thioxanthenone, a new class of photodetritylating agents for microarray oligonucleotide synthesis].

The usability of a new class of photo acids, namely, sulfonium hexaphosphates based on thioxanthenone, for the removal of the dimethoxytrityl protective group in the process of oligonucleotide synthesis has been studied in order to search for new detritylating agents for microarray oligodeoxyribonucleotide synthesis. 2,4-Diethyl-9-oxo-10-(4-heptyloxyphenyl)-9H-thioxanthenium hexafluorophosphate has been successfully used for the solid-phase synthesis of (dT)(10).

[Frequency of RET/PTC rearrangement and somatic BRAF mutation in papillary thyroid cancer].

Frequency of RET/PTC rearrangement and somatic BRAF mutation was investigated in patients with papillary thyroid cancer (PTC) vis-a-vis relevant demographic and clinico-pathological features. The study group included 76 patients with a female/male ratio of 4.8:1; mean age - 45.7 +/- 9.7 yrs. BRAF mutation was identified in 49 (65%) (V600E--47, KSRWS600--1 and E585K--1). RET rearrangement was detected in 9 (12%): RET/PTC1--5, RET/PTC3--2, unspecified RET/PTC--1 and delta RET/PTC--1. It was age at diagnosis alone that proved to be consistently associated with BRAF mutations (p = 0.017). Younger tumor patients were mostly prone to RET/PTC rearrangement (p = 0.08). No correlation between mutation and clinico-pathological features was established.

[Abnormal methylation of p16/CDKN2A AND p14/ARF genes GpG Islands in non-small cell lung cancer and in acute lymphoblastic leukemia]. / Sravnitel'nyi analiz anomal'nogo metilirovaniia CpG-ostrovkov, raspolozhennykh v promotornykh oblastiakh genov p16/CDKN2A i p14/ARF, pri nemelkokletochnom rake legkogo i ostrom limfoblastnom leikoze.

Multiplex methylation-sensitive PCR and methylation-specific PCR were employed in studying the methylation of CpG islands in the p16/CDKN2A and p14/ARF promoter and the first exon regions in non-small cell lung cancer (54 samples) and acute B-cell lymphoblastic leukemia (61 samples). Differences in methylation were detected between types of neoplasia as well as between CpG islands studied within the same types of tumors. High level of the p16/CDKN2A first exon CpC island methylation was revealed in non-small cell lung cancer (68%) and in acute B-cell lymphoblastic leukemia (55%) and the CpG island of p14/ARF first exon was nonmethylated in these types of tumors. The methylation of CpG-rich fragments of genes p16/CDKN2A and p14/ARF promoters was analysed. As was found out, CpG islands located in 5' areas of one and the same gene can differ in methylation frequencies. The comparison of sensitivity between methylation-specific PCR and methylation-sensitive PCR used in the methylations studies was carried out.

[Molecular analysis of structural abnormalities in papillary thyroid carcinoma gene]. / Molekuliarnyi analiz strukturnykh narushenii genoma papilliarnykh kartsinom shchitovidnoi zhelezy.

Rearrangements of the RET proto-oncogene (RET/PTC) and BRAF gene mutations are the major genetic alterations in the etiopathogenesis of papillary thyroid carcinoma (PTC). We have analyzed a series of 118 benign and malignant follicular cell-derived thyroid tumors for RET/PTC rearrangements and BRAF gene mutations. Oncogenic rearrangements of RET proto-oncogene was revealed by semiquantitative RT-PCR of simultaneously generated fragments corresponding to tyrosine kinase (TK) and extracellular RET domains. The clear quantitative shift toward the TK fragment is indicative for the presence of RET rearrangements. The overall frequency of RET/PTC rearrangements in PTC was 14% (12 of 85), including 7 RET/PTC1, 2 RET/PTC3, 1 deltaRFP/RET and 2 apparently uncharacterized rearrangements. The most common T1796A transversion in BRAF gene was detected in 55 of 91 PTC (60%) using mutant-allele-specific PCR. We also identified two additional mutations: the substitution G1753A (E585K) and a case of 12-bp deletion in BRAF exon 15. Moreover, there was no overlap between PTC harboring BRAF and RET/PTC mutations, which altogether were present in 75.8% of cases (69 of 91). Taken together, our observations are consistent with the notion that BRAF mutations appear to be an alternative pathway to oncogenic MAPK activation in PTCs without RET/PTC activation. Neither RET/PTC rearrangements nor BRAF muta-tions were detected in any of 3 follicular thyroid carcinomas, 11 follicular adenomas and 13 nodular goiters. The high prevalence of BRAF mutations and RET/PTC rearrangements in PTCs and the specificity of these alterations to PTC make them potentially important markers for the preoperative tumor diagnosis.

[Diagnostics for epigenetic pathology in hereditary and oncologic diseases]. / Diagnostika épigeneticheskoi patologii pri nasledstvennykh i onkologicheskikh zabolevaniiakh.

The review considers the epigenetic defects and their diagnostics in several hereditary disorders and tumors. Aberrant methylation of the promoter or regulatory region of a gene results in its functional inactivation, which is phenotypically similar to structural deletion. Screening tests were developed for Prader-Willi, Angelman, Wiedemann-Beckwith, and Martin-Bell syndromes and mental retardation FRAXE. The tests are based on allele methylation analysis by methylation-specific or methylation-sensitive PCR. Carcinogenesis-associated genes (RB1, CDKN2A, ARF14, HIC1, CDI, etc.) are often methylated in tumors. Tumors differ in methylation frequencies, allowing differential diagnostics. Aberrant methylation of tumor suppressor genes occurs in early carcinogenesis, and its detection may be employed in presymptomatic diagnostics of tumors.

[Diagnosis and treatment of syndrome of multiple endocrine neoplasia type 2]. / Diagnostika i lechenie sindroma mnozhestvennykh éndokrinnykh neoplazii 2-go tipa.

Since 1969 to 2000 twenty one patients from 16 families with syndrome of multiple endocrine neoplasia (MEN) type 2 were examined. Medullary cancer of the thyroid gland (MCTG) was diagnosed in 18 patients, pheochromocytoma--in 15 (in 13 of them--two-sided), primary hyperparathyroidism--in 2. In 9 patients from 5 families syndrome MEN 2 was confirmed genetically (mutation in codon 634 of 11th exon RET in 7 patients with MEN 2a and in codon 918 in 2 patients with MEN 2b). None of the patients had extraadrenal pheochromocytoma, in 9 (60%) patients multicentric tumors within one adrenal gland were diagnosed. All the 18 patients with MCTG underwent extrafascial thyroidectomy with removal of fat and lymph nodes of paratracheal zone, 9 patients--one-sided (6) or two-sided (3) removal of fat and lymph nodes of lateral triangle of neck. Prophylactic thyreoidectomy was performed in 11-year old patient with genetically verified MEN 2a and without topical data of MCTG, 2 patients of 3 and 19 years of age with genetically verified MEN 2 are to undergo prophylactic thyroidectomy. Prophylactic thyroidectomy is necessary in the presence of genetic disorders in members of families with MEN 2 despite absence of structural changes in thyroid gland. Level of basal and stimulated calcitonin may be used as marker of recurrence or metastatic growth only. In MEN 2 after organ-saving operation rate of true recurrence of tumor is high because of genetic damage of medullary layer of adrenal gland.