Basal cell carcinomas acquire secondary mutations to overcome dormancy and progress from microscopic to macroscopic disease.

Basal cell carcinomas (BCCs) frequently possess immense mutational burdens; however, the functional significance of most of these mutations remains unclear. Here, we report that loss of Ptch1, the most common mutation that activates upstream Hedgehog (Hh) signaling, initiates the formation of nascent BCC-like tumors that eventually enter into a dormant state. However, rare tumors that overcome dormancy acquire the ability to hyperactivate downstream Hh signaling through a variety of mechanisms, including amplification of Gli1/2 and upregulation of Mycn. Furthermore, we demonstrate that MYCN overexpression promotes the progression of tumors induced by loss of Ptch1. These findings suggest that canonical mutations that activate upstream Hh signaling are necessary, but not sufficient, for BCC to fully progress. Rather, tumors likely acquire secondary mutations that further hyperactivate downstream Hh signaling in order to escape dormancy and enter a trajectory of uncontrolled expansion.

Facilitators and barriers to allyship in academic surgery: A qualitative study.

BACKGROUND: Academic health centers have promoted initiatives to improve diversity, equity and inclusion in medicine. Despite this emphasis, there has been limited discussion on practical strategies for navigating bias within academic surgery. This study analyzes experiences of confronting bias within the department of surgery at the University of Michigan. MATERIALS AND METHODS: We conducted telephone interviews (n = 15) from January 2019 to January 2020 with surgeon volunteers at one academic institution. Two investigators conducted interviews following a semi-structured guide based on personal experiences with bias between healthcare workers with diverse identities. Interviews were conducted concurrently with thematic coding, coded independently by two investigators, and discussed until consensus was reached. Analysis proceeded following the inductive and comparative approach of interpretive description. RESULTS: The most common incidents of bias were based on gender and race. They occurred along numerous relationship axes, including physician-patient and resident-faculty. A critical factor in bias response was unambiguously recognizing bias. Responding to bias consists of timing and nature of the response, defined as when the subject responded relative to the incident and the actions done in response to the incident respectively. Barriers to bias response were fear of retribution and extensive energy required to respond. Institutional culture was important, specifically in representation and support from peers and administration. CONCLUSIONS: This study probes deeper into equity and inclusivity in the academic field of surgery, offering insight into common barriers to confronting bias. Overall, these findings offer a basic framework for allies to identify bias and to partner with colleagues to address biases in a supportive manner.