1,721,226 research outputs found
Hurthle tumors: a class of thyroid malignancy with massive chromosome disturbance
No full textGanly et al. have recently provided elegant evidence that Hurthle cell carcinoma (1), an understudied thyroid cancer characterized by > 75% large cells with hyperchromatic nuclei and a granular cytoplasm extraordinarily rich in mitochondria, constitutes a unique class of thyroid cancer.
Using a global approach, including mass spectrometry-based genotyping, array comparative genomic hybridization, and expression profiling, the authors demonstrated that mutational, transcriptional, and copy number profiles of this tumor are distinct from both papillary and follicular carcinoma. In particular, the authors highlighted that the striking feature was the finding of large regions of gain on chromosomes 5, 7, 12, and 17, suggesting the presence of chromosomal instability or selection for increased copies of specific chromosomes.
These data are in line with our early observations in thyroid oncocytic neoplasms obtained by conjugating immunofluorescence and fluorescence in situ hybridization approaches (2). Single cell fluorescent immunophenotyping with an anti-mitochondrion antibody followed by FISH with centromeric DNA probes for different chromosomes not only supported our conventional G-banding and CGH results, indicating presence of chromosome gains in oncocytic follicular lesions, but substantiated that chromosome changes in Hurthle carcinoma (oncocytic variant of follicular tumors, according to the World Health Organization) were confined to the mitochondrion-rich cells. In addition, we reported that among mitochondrion-rich carcinomas only the Hurthle variant showed numerical chromosome gains, whereas the oncocytic papillary tumors were diploid. A different distribution of mitochondria between the Hurthle carcinoma and the papillary oncocytic carcinoma was also observed, the former exhibiting diffuse distribution, the latter exhibiting polar.
Karyotypic and molecular cytogenetic data (2, 3) also indicated that trisomy 7 is the first numerical aberration to occur, and that numerical changes seem to accumulate according to an evolutionary scheme. We also observed that oncocytic lesions not defined as Hurthle tumor (because they contained fewer than 75% oncocytes) showed chromosome numerical changes. Based on these observations, we hypothesized that trisomy 7 may confer a proliferative advantage, priming the “cascade” of alterations with selection of cells prone to progressively accumulate specific chromosomes and mitochondria.
This speculation is also consistent with the Ganly group's observation on the absence of any pattern of chromosomal gains/losses that could specifically differentiate Hurthle adenoma (by definition having > 75% oncocytic cells) from minimally and widely invasive tumors. According to our hypothesis, in fact, accumulation of chromosome numerical changes and mitochondria starts in lesions with a low percentage of oncocytes, and trisomy 7 would possibly be implicated in the mitochondria accumulation process. This led us to support the contention that follicular tumors composed of oncocytes should be regarded as a distinct subset.
In our view, the Ganly report has meaningful value, adding new, conclusive evidence that the Hurthle neoplasm represents a unique class of thyroid malignancy.
References
Ganly I, Ricarte Filho J, Eng S, Ghossein R, Morris LG, Liang Y, Socci N, Kannan K, Mo Q, Fagin JA, Chan TA. Genomic dissection of Hurthle cell carcinoma reveals a unique class of thyroid malignancy. J Clin Endocrinol Metab 2013; 98:E962–E972
Dettori T, Frau DV, Lai ML, Mariotti S, Uccheddu A, Daniele GM, Tallini G, Faa G, Vanni R. Aneuploidy in oncocytic lesions of the thyroid gland: diffuse accumulation of mitochondria within the cell is associated with trisomy 7 and progressive numerical chromosomal alterations. Genes Chromosomes Cancer 2003;38:22–31
Belge G, Thode B, Rippe V, Bartnitzke S, Bullerdiek J. A characteristic sequence of trisomies starting with trisomy 7 in benign thyroid tumors. Hum Genet 1994; 94:198–20
Epidermal growth factor receptor (EGFR) targeted therapies in non-small cell lung cancer (NSCLC).
No full textMetro G, Finocchiaro G, Toschi L, Bartolini S, Magrini E, Cancellieri A, Trisolini R, Castaldini L, Tallini G, Crino' L, Cappuzzo F. Epidermal growth factor receptor (EGFR) targeted therapies in non-small cell lung cancer (NSCLC). Reviews on recent clinical trials. 2006;1:1-13
Molecular Pathology of Poorly Differentiated and Anaplastic Thyroid Cancer: What Do Pathologists Need to Know?
Full text linkThe molecular characterization of poorly and anaplastic thyroid carcinomas has been greatly improved in the last years following the advent of high throughput technologies. However, with special reference to genomic data, the prevalence of reported alterations is partly affected by classification criteria. The impact of molecular pathology in these tumors is multifaceted and bears diagnostic, prognostic, and predictive implications although its use in the clinical practice is not completely assessed. Genomic profiling data claim that genetic alterations in poorly differentiated and anaplastic thyroid carcinomas include “Early” and “Late” molecular events, which are consistent with a multi-step model of progression. “Early” driver events are mostly RAS and BRAF mutations, whereas “Late” changes include above all TP53 and TERT promoter mutations, as well as dysregulation of gene involved in the cell cycle, chromatin remodeling, histone modifications, and DNA mismatch repair. Gene fusions are rare but represent relevant therapeutic targets. Epigenetic modifications are also playing a relevant role in poorly differentiated and anaplastic thyroid carcinomas, with altered regulation of either genes by methylation/deacetylation or non-coding RNAs. The biological effects of epigenetic modifications are not fully elucidated but interfere with a wide spectrum of cellular functions. From a clinical standpoint, the combination of genomic and epigenetic data shows that several molecular alterations affect druggable cellular pathways in poorly differentiated and anaplastic thyroid carcinomas, although the clinical impact of molecular typing of these tumors in terms of predictive biomarker testing is still under exploration
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
What is new in thyroid cancer: The special issue of the journal cancers
Full text linkThe incidence of thyroid cancer has increased over the past 3 to 4 decades. Nonetheless, the mortality from thyroid cancer has remained stable. The thyroid gland may develop nodules encompassing several types of cell proliferation, from frankly benign to very aggressive forms with many intermediate challenging variants. For this reason, there is growing interest in evaluating thyroid nodules from many points of view, from the clinical to the molecular aspects, in the search for innovative diagnostic and prognostic parameters. The aim of this Special Issue was to provide an overview of recent developments in understanding the biology and molecular oncology of thyroid tumors of follicular cell derivation and their repercussions on the diagnosis, prognosis, and therapy. The contributions of many experts in the field made up a Special Issue of Cancers journal, that focusing on different aspects, including mechanistic and functional facets, gives the status of art of clinical and biological perspectives of thyroid cancer
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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