Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1. Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1

Deploying culture as a defence against incompetence: The unconscious dynamics of public service work

Orientation: The intractability of public service delivery and a polarised societal landscape heighten anxiety and reinforce a propensity for public service organisations to be used for defensive purposes. Research purpose: This article employs social defense theory to explore manifestations of anxiety and defense within South African public service organisations. Motivation for the study: Dominant discourse on public service institutions over-relies on political, sociological and public administration theories and tends to ignore psychosocial explanations. Further, whilst the psychodynamics of social service work are generally understood, the unconscious dynamics of generic public service work remain under-theorised. Research design, approach and method: This conceptual article draws on my personal observations as a reflective citizen and experiences as a consultant to government departments. Main findings: Herein, an argument is advanced that the deployment of ill-qualified party loyalists to key positions in the public service is perverse: it serves as a collective defense against the impossible aspects of the task at hand. The appointees, in turn, deploy organisational processes to defend against feelings of incompetence and the inevitability of failure. This practice, coupled with acute resource constraints, sets up front line staff for scapegoating. Practical/managerial implications: An appreciation of the multiple meanings of public service work and the defensive role played by public institutions stands to inform purposeful change towards sustainable public service organisational practice. Contribution/value-add: The discussion seeks to contribute to attempts that employ systems psychodynamics to make sense of anxiety and defense within organisations in general and public service institutions in particular

Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1. Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1