Complex rearrangements fuel ER and HER2 breast tumours.

Breast cancer is a highly heterogeneous disease whose prognosis and treatment as defined by the expression of three receptors-oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 (HER2; encoded by ERBB2)-is insufficient to capture the full spectrum of clinical outcomes and therapeutic vulnerabilities. Previously, we demonstrated that transcriptional and genomic profiles define eleven integrative subtypes with distinct clinical outcomes, including four ER subtypes with increased risk of relapse decades after diagnosis. Here, to determine whether these subtypes reflect distinct evolutionary histories, interactions with the immune system and pathway dependencies, we established a meta-cohort of 1,828 breast tumours spanning pre-invasive, primary invasive and metastatic disease with whole-genome and transcriptome sequencing.

Single-cell spatial mapping reveals alteration of cell type composition and tissue microenvironment during early colorectal cancer formation.

Colorectal cancer (CRC) is the third leading cause of cancer mortality in the United States. Familial adenomatous polyposis (FAP) is a hereditary syndrome that raises the risk of developing CRC, with total colectomy as the only effective prevention. Even though FAP is rare (0.

Cancers adapt to their mutational load by buffering protein misfolding stress.

In asexual populations that don't undergo recombination, such as cancer, deleterious mutations are expected to accrue readily due to genome-wide linkage between mutations. Despite this mutational load of often thousands of deleterious mutations, many tumors thrive. How tumors survive the damaging consequences of this mutational load is not well understood.

The Impact of Socioeconomic Status on Pediatric Facial Trauma.

Study Design: Retrospective chart review.

Objective: Socioeconomic status (SES) greatly impacts one's health status and the type of trauma that a patient experiences due to increased risk of exposure and varying availability of resources to treat emergent conditions. There is a need for large-scale databases of pediatric facial trauma to identify discrepancies in occurrence and identify risk factors.

In vitro vascularization improves in vivo functionality of human engineered cardiac tissues.

Engineered human cardiac tissues hold great promise for disease modeling, drug development, and regenerative therapy. For regenerative applications, successful engineered tissue engraftment in vivo requires rapid vascularization and blood perfusion post-implantation. In the present study, we engineered highly functional, vascularized cardiac tissues ("cardiopatches") by co-culturing human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) and endothelial cells (hiPSC-ECs) in optimized serum-free media.