Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous largescale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.Cancer forms and progresses through a series of critical transitions-from pre-malignant to malignant states, from locally contained to metastatic disease, and from treatment-responsive to treatment-resistant tumors (Figure 1). Although specifics differ across tumor types and patients, all transitions involve complex dynamic interactions between diverse pre-malignant, malignant, and non-malignant cells (e.g., stroma cells and immune cells), often organized in specific patterns within the tumor

This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

Background & Aims As traditional methods have become increasingly difficult, the Internet offers a mechanism for conducting survey research quickly and efficiently. The validity of this research, however, depends on the ability of respondents to accurately report health status. We used a large Internet-based inflammatory bowel disease cohort to validate self-reported IBD against physician reports. Methods Between 06/22/2012 and 04/01/13, all CCFA Partners participants (n=6681) were invited to participate and 450 were selected by random stratified sampling. We sent physicians a survey to confirm IBD diagnosis and characteristics. We used descriptive statistics to compare data. Results A total of 4423 (66%) participants indicated interest. Of 450 selected, 261 (58%) consented and physician reports were obtained for 184 (71%). Physicians confirmed IBD status in 178 (97%) and type in 171 (97% of confirmed). The matching between patient and physician reports for Crohn’s disease (CD) was 82% for disease location, 89% for presence of perianal disease and 46% for disease behavior. For ulcerative colitis (UC), disease location matched 54% of the time. Physician reports confirmed the status of ever having bowel surgery for 97% of CD and 94% for UC, and confirmed current pouch or ostomy in 84% of CD and 81% of UC. Discussion Self-reported IBD in CCFA Partners is highly accurate and participants are willing to release medical records for research. Self-reported phenotypic characteristics were less valid. The validity of IBD diagnoses among CCFA Partners participants supports the use of this cohort for patient centered outcomes research.

GOALS To determine the role of NSAIDs in activation of IBD. BACKGROUND Non-steroidal anti-inflammatory drugs (NSAIDs) may activate inflammatory pathways in inflammatory bowel disease (IBD). STUDY Crohn’s and Colitis Foundation of American (CCFA) Partners is an ongoing cohort study of patients living with IBD. All data are self-reported via the internet. We identified a sub-cohort of participants whose disease activity, based on short Crohn’s Disease Activity Index (sCDAI) and simple clinical colitis activity index (SCCAI), indicated remission. Pattern of use of NSAIDs was measured at baseline, and disease activity assessment was performed 6 months later. We used multivariate binomial regression to determine effects of NSAIDs on disease activity. RESULTS A total of 791 individuals in remission had baseline and follow data available for analysis. Of these, 247 Crohn’s disease (CD) patients (43.2%) and 89 ulcerative colitis (UC) patients (40.6%) reported NSAID use. CD patients with NSAID use ≥ 5 times/monthly had greater risk of active disease at follow-up (23% v. 15%, p=0.04); (adjusted risk ratio (RR) 1.65; 95% confidence interval (CI) 1.12–2.44). No effect was observed in patients with UC (22% vs 21%, p=0.98; adjusted RR 1.25; 95% CI, 0.81–1.92). Acetaminophen use was associated with active disease at follow-up in CD (adjusted RR 1.72, 95% CI 1.11–2.68). CONCLUSIONS Regular (≥ 5 times/monthly) NSAID and acetaminophen use were associated with active CD, but not UC. Less frequent NSAID use was not associated with active CD or UC. These findings indicate that regular NSAID use may increase CD activity, or that NSAID use may be a marker of a less robust remission; thus reflecting subclinical disease activity.