The Progenetix oncogenomic resource in 2021.

In cancer, copy number aberrations (CNAs) represent a type of nearly ubiquitous and frequently extensive structural genome variations. To disentangle the molecular mechanisms underlying tumorigenesis as well as identify and characterize molecular subtypes, the comparative and meta-analysis of large genomic variant collections can be of immense importance. Over the last decades, cancer genomic profiling projects have resulted in a large amount of somatic genome variation profiles, however segregated in a multitude of individual studies and datasets. The Progenetix project, initiated in 2001, curates individual cancer CNA profiles and associated metadata from published oncogenomic studies and data repositories with the aim to empower integrative analyses spanning all different cancer biologies. During the last few years, the fields of genomics and cancer research have seen significant advancement in terms of molecular genetics technology, disease concepts, data standard harmonization as well as data availability, in an increasingly structured and systematic manner. For the Progenetix resource, continuous data integration, curation and maintenance have resulted in the most comprehensive representation of cancer genome CNA profiling data with 138 663 (including 115 357 tumor) copy number variation (CNV) profiles. In this article, we report a 4.5-fold increase in sample number since 2013, improvements in data quality, ontology representation with a CNV landscape summary over 51 distinctive National Cancer Institute Thesaurus cancer terms as well as updates in database schemas, and data access including new web front-end and programmatic data access. Database URL: progenetix.org.

Geographic assessment of cancer genome profiling studies.

Cancers arise from the accumulation of somatic genome mutations, which can be influenced by inherited genomic variants and external factors such as environmental or lifestyle-related exposure. Due to the heterogeneity of cancers, precise information about the genomic composition of germline and malignant tissues has to be correlated with morphological, clinical and extrinsic features to advance medical knowledge and treatment options. With global differences in cancer frequencies and disease types, geographic data is of importance to understand the interplay between genetic ancestry and environmental influence in cancer incidence, progression and treatment outcome. In this study, we analyzed the current landscape of oncogenomic screening publications for geographic information content and quality, to address underrepresented study populations and thereby to fill prominent gaps in our understanding of interactions between somatic variations, population genetics and environmental factors in oncogenesis. We conclude that while the use of proxy-derived geographic annotations can be useful for coarse-grained associations, the study of geo-correlated factors in cancer causation and progression will benefit from standardized geographic provenance annotations. Additionally, publication-derived geographic provenance data allowed us to highlight stark inequality in the geographies of cancer genome profiling, with a near lack of sizable studies from Africa and other large regions.

Mountains and Chasms: Surveying the Oncogenomic Publication Landscape.

Cancers arise from the accumulation of somatic genome mutations, with varying contributions of intrinsic (i.e., genetic predisposition) and extrinsic (i.e., environmental) factors. For the understanding of malignant clones, precise information about their genomic composition has to be correlated with morphological, clinical, and individual features in the context of the available medical knowledge. Rapid improvements in molecular profiling techniques, the accumulation of a large amount of data in genomic alterations in human malignancies, and the expansion of bioinformatic tools and methodologies have facilitated the understanding of the molecular changes during oncogenesis, and their correlation with clinicopathological phenotypes. Far beyond a limited set of "driver" genes, oncogenomic profiling has identified a large variety of somatic mutations, and whole-genome sequencing studies of healthy individuals have improved the knowledge of heritable genome variation. Nevertheless, the main challenges arise from the skewed representation of individuals from varying population backgrounds in biomedical studies, and also through the limited extent in which some cancer entities are represented in the scientific literature. Content analyses of oncogenomic publications could provide guidance for the planning and support of future studies aiming at filling prominent knowledge gaps.