Telomerase promoter mutations in cancer: an emerging molecular biomarker?

João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the “alternative mechanism of telomere lengthening” (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.ope

Andrew M. Pettigrew : a groundbreaking process scholar

This chapter positions Andrew Pettigrew as a process scholar. It describes his work of catching “reality in flight” as he investigated the continuity and change, which is involved in subject areas like the politics of organizational decision-making, organizational culture, fundamental strategic change, human resource management, competitiveness, the workings of boards of directors, and new organizational forms. The chapter also describes the research methodology of contextualism that Andrew Pettigrew developed to capture “reality in flight.” It discusses the extent to which Andrew Pettigrew succeeded and how his research program could be developed further

Would Plato Have Banned the Management Consultants?

© 2020, Springer Nature Switzerland AG. Plato decided that the poets, that is, all creative writers, should be banned from his ideal state. He objected to the claim that they imparted knowledge to their audiences. The poets gave no explanation of the basis for the stories that they told or the conclusions to which those stories led. Plato denied the validity of any claim to knowledge that was not accompanied by an account that justified the claim. Management scholars make comparable objections to management consultants. They argue that consultants use rhetoric and story-telling to persuade clients of their knowledge, when their services often have no foundation in real knowledge. Consultancy knowledge is to a large extent socially constructed, dependent for its status as knowledge on clients’ acceptance of it as such. Consultants often sell their services and persuade clients of their value by appealing to their relevance to passing management fashions and fads. The poets necessarily are susceptible to Plato’s objections, because they are creative artists whose proper business is primarily to entertain rather than to impart knowledge. By contrast, consultants have a clear role in imparting and applying management knowledge. They should respond to management scholars’ objections by shifting their focus ever more sharply towards the technoeconomic contributions that consultants can make to their clients, and away from the use of rhetoric and story-telling to promote their services