A role for SETD2 loss in tumorigenesis through DNA methylation dysregulation

SETD2-dependent H3 Lysine-36 trimethylation (H3K36me3) has been recently linked to the deposition of de-novo DNA methylation. SETD2 is frequently mutated in cancer, however, the functional impact of SETD2 loss and depletion on DNA methylation across cancer types and tumorigenesis is currently unknown. Here, we perform a pan-cancer analysis and show that both SETD2 mutation and reduced expression are associated with DNA methylation dysregulation across 21 out of the 24 cancer types tested. In renal cancer, these DNA methylation changes are associated with altered gene expression of oncogenes, tumour suppressors, and genes involved in neoplasm invasiveness, including TP53, FOXO1, and CDK4. This suggests a new role for SETD2 loss in tumorigenesis and cancer aggressiveness through DNA methylation dysregulation. Moreover, using a robust machine learning methodology, we develop and validate a 3-CpG methylation signature which is sufficient to predict SETD2 mutation status with high accuracy and correlates with patient prognosis

The contribution of financial entities to the sustainable development through the reporting of corporate social responsibility information

This paper aims at examining the relationship between board composition and corporate social responsibility (CSR) of a sample of listed financial entities, discussing the driving reasons of these entities to disclose CSR information. We hypothesize that there is a positive association between outside (institutional and independent directors) and female directors and CSR disclosure and a negative relationship between inside directors and CSR reporting. Our findings provide evidence that the proportions of independent directors and female directors on boards encourage CSR disclosure. Moreover, the results also show that the proportions of inside directors and institutional directors on boards do not have influence on CSR reporting. Thus, our evidence suggests that board attributes such as independent and female directors encourage financial entities to report CSR matters, showing the effectiveness of these two corporate governance mechanisms. The paper shed light on the influence of board structure of financial entities on CSR disclosure. Therefore, this study contributes to past research by providing an index to measure CSR disclosure of financial entities and the importance of the distinction between outside and inside directors