Особенности фолликулярной аденомы и фолликулярного рака щитовидной железы у детей

În urma investigaţiilor histologice grupul de autori a descoperit diferenţe în grosimea capsulei tumorale în adenom folicular şi în cancer folicular. Astfel, în 77,5% cazuri de adenom folicular capsula în jurul nodulului tumoral era subţire, iar în cancerul, folicular ea era mai groasă. Diagnosticul exact, stabilit în perioada preoperatorie, le-a permis autorilor să efectueze operaţii adecvate în funcţie de tipul tumorii.Особенности фолликулярной аденомы и фолликулярного рака щитовидной железы у дете

Опухолевые стволовые клетки при раке молочной железы. Роль в патогенезе и подходы к терапии

The breast cancer takes the leading position among all women cancers in the world and the Russian Federation. Despite great advances in treatment, unfortunately, distant metastasis of breast cancer may develop in patients at early stages of disease. This phenomenon can be explained by the new theory of tumor stem cells, capable of an unlimited period of time to share and support the development of a primary tumor. This review presents the concept of tumor stem cells, their clinical and prognostic significance in the breast cancer pathogenesis, the impact on the development of resistance to cytotoxic drugs and prospects for new and effective strategies and approaches to systemic anticancer therapy for breast cancer.Рак молочной железы занимает лидирующее место среди всех онкологических заболеваний у женщин в мире, в т. ч. и в России. Несмотря на большие достижения в комплексном лечении, к сожалению, отдаленные метастазы рака молочной железы могут развиваться у больных на ранних стадиях заболевания. Данный феномен может быть объяснен новой теорией опухолевых стволовых клеток, способных в течение неограниченного периода времени делиться и поддерживать дальнейшее развитие первичной опухоли. В настоящем обзоре представлены концепция опухолевых стволовых клеток, их клиническое и прогностическое значение в патогенезе рака молочной железы, влияние на развитие резистентности к цитостатическим препаратам, а также перспективы новых и эффективных стратегий и подходов к системной противоопухолевой терапии рака молочной железы

Myosin 1C isoform A is a novel candidate diagnostic marker for prostate cancer.

Early diagnosis of prostate cancer is a challenging issue due to the lack of specific markers. Therefore, a sensitive diagnostic marker that is expressed or upregulated exclusively in prostate cancer cells would facilitate diagnostic procedures and ensure a better outcome. We evaluated the expression of myosin 1C isoform A in 5 prostate cell lines, 41 prostate cancer cases, and 11 benign hyperplasias. We analyzed the expression of 12 surface molecules on prostate cancer cells by flow cytometry and analyzed whether high or low myosin 1C isoform A expression could be attributed to a distinct phenotype of prostate cancer cells. Median myosin 1C isoform A expression in prostate cancer samples and cancer cell lines was 2 orders of magnitude higher than in benign prostate hyperplasia. Based on isoform A expression, we could also distinguish clinical stage 2 from clinical stage 3. Among cell lines, PC-3 cells with the highest myosin 1C isoform A level had diminished numbers of CD10/CD13-positive cells and increased numbers of CD29 (integrin β1), CD38, CD54 (ICAM1) positive cells. The surface phenotype of clinical samples was similar to prostate cancer cell lines with high isoform A expression and could be described as CD10-/CD13- with heterogeneous expression of other markers. Both for cell lines and cancer specimens we observed the strong correlation of high myosin 1C isoform A mRNA expression and elevated levels of CD29 and CD54, suggesting a more adhesive phenotype for cells with high isoform A expression. Compared to normal tissue, prostate cancer samples had also reduced numbers of CD24- and CD38-positive cells. Our data suggest that a high level of myosin 1C isoform A is a specific marker both for prostate cancer cells and prostate cancer cell lines. High expression of isoform A is associated with less activated (CD24/CD38 low) and more adhesive (CD29/CD54 high) surface phenotype compared to benign prostate tissue

Genetic Programming of Hypertension

The heritability of hypertension (HTN) is widely recognized and as a result, extensive studies ranging from genetic linkage analyses to genome-wide association studies are actively ongoing to elucidate the etiology of both monogenic and polygenic forms of HTN. Due to the complex nature of essential HTN, however, single genes affecting blood pressure (BP) variability remain difficult to isolate and identify and have rendered the development of single-gene targeted therapies challenging. The roles of other causative factors in modulating BP, such as gene–environment interactions and epigenetic factors, are increasingly being brought to the forefront. In this review, we discuss the various monogenic HTN syndromes and corresponding pathophysiologic mechanisms, the different methodologies employed in genetic studies of essential HTN, the mechanisms for epigenetic modulation of essential HTN, pharmacogenomics and HTN, and finally, recent advances in genetic studies of essential HTN in the pediatric population

Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas

BACKGROUND Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas. METHODS We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes. RESULTS Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma. CONCLUSIONS The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to glioblastomaclose

Integrated genomic characterization of endometrial carcinoma

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ~25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.National Institutes of Health (U.S.) (Grant 5U24CA143799-04)National Institutes of Health (U.S.) (Grant 5U24CA143835-04)National Institutes of Health (U.S.) (Grant 5U24CA143840-04)National Institutes of Health (U.S.) (Grant 5U24CA143843-04)National Institutes of Health (U.S.) (Grant 5U24CA143845-04)National Institutes of Health (U.S.) (Grant 5U24CA143848-04)National Institutes of Health (U.S.) (Grant 5U24CA143858-04)National Institutes of Health (U.S.) (Grant 5U24CA143866-04)National Institutes of Health (U.S.) (Grant 5U24CA143867-04)National Institutes of Health (U.S.) (Grant 5U24CA143882-04)National Institutes of Health (U.S.) (Grant 5U24CA143883-04)National Institutes of Health (U.S.) (Grant 5U24CA144025-04)National Institutes of Health (U.S.) (Grant U54HG003067-11)National Institutes of Health (U.S.) (Grant U54HG003079-10)National Institutes of Health (U.S.) (Grant U54HG003273-10

Comprehensive molecular profiling of lung adenocarcinoma

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen(mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis

Comprehensive molecular profiling of lung adenocarcinoma

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen(mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesisclose24

Comprehensive molecular profiling of lung adenocarcinoma: the cancer genome atlas research network

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis