Generation of in situ sequencing based OncoMaps to spatially resolve gene expression profiles of diagnostic and prognostic markers in breast cancer

Background: Gene expression analysis of breast cancer largely relies on homogenized tissue samples. Due to the high degree of cellular and molecular heterogeneity of tumor tissues, bulk tissue-based analytical approaches can only provide very limited system-level information about different signaling mechanisms and cellular interactions within the complex tissue context. Methods: We describe an analytical approach using in situ sequencing (ISS), enabling highly multiplexed, spatially and morphologically resolved gene expression profiling. Ninety-one genes including prognostic and predictive marker profiles, as well as genes involved in specific cellular pathways were mapped within whole breast cancer tissue sections, covering luminal A/B-like, HER2-positive and triple negative tumors. Finally, all these features were combined and assembled into a molecular-morphological OncoMap for each tumor tissue. Findings: Our in situ approach spatially revealed intratumoral heterogeneity with regard to tumor subtype as well as to the OncotypeDX recurrence score and even uncovered areas of minor cellular subpopulations. Since ISS-resolved molecular profiles are linked to their histological context, a deeper analysis of the core and periphery of tumor foci enabled identification of specific gene expression patterns associated with these morphologically relevant regions. Interpretation: ISS generated OncoMaps represent useful tools to extend our general understanding of the biological processes behind tumor progression and can further support the identification of novel therapeutical targets as well as refine tumor diagnostics. Fund: Swedish Cancerfonden, UCAN, Vetenskapsrådet, Cancer Genomics Netherlands, Iris, Stig och Gerry Castenbäcks Stiftelse, BRECT, PCM Program, King Gustaf V Jubilee Fund, BRO, KI and Stockholm County Council, Alice Wallenberg Foundation

An Assessment of the Growth Debate: A Comparison of Perspectives

The debate on growth versus environment, including the more recent literature on sustainable development, is systematically evaluated in a stylized framework. Diffent perspectives on the conflict and relation between the economy, growth and the natural environment, have created a situation where people do not talk the same language. A conceptual framework is developed which allows to explain main diffences between alternative perspectives. Five categories are distinguished, labelled as: "the immaterialist", "the pessimist", "the technocrat", "carpe diem" and "the optimist". Both the conceptual framework and a set of characteristics (time horizon, ideology, prediction and policy implication) are used to compare these perspectives. Primarily the choice of a time horizon and the subjective evaluation of technical potential, the flexibility of social preferences and institutions, and the stability and resilience of natural systems, explain differences between the perspectives. Such a systematic confrontation is hoped to contribute to more consensus and understanding between supporters of alternative perspectives