Unscrambling cancer genomes via integrated analysis of structural variation and copy number

Complex somatic genomic rearrangements and copy number alterations are hallmarks of nearly all cancers. We have developed an algorithm, LINX, to aid interpretation of structural variant and copy number data derived from short-read, whole-genome sequencing. LINX classifies raw structural variant calls into distinct events and predicts their effect on the local structure of the derivative chromosome and the functional impact on affected genes. Visualizations facilitate further investigation of complex rearrangements. LINX allows insights into a diverse range of structural variation events and can reliably detect pathogenic rearrangements, including gene fusions, immunoglobulin enhancer rearrangements, intragenic deletions, and duplications. Uniquely, LINX also predicts chained fusions that we demonstrate account for 13% of clinically relevant oncogenic fusions. LINX also reports a class of inactivation events that we term homozygous disruptions that may be a driver mutation in up to 9% of tumors and may frequently affect PTEN, TP53, and RB1

What to Do With That Policy Paper (and Why)

In this editorial we describe the clinician/administrator/researcher experience of frustration or confusion around how to effectively advocate for policy change in health care. By the end of the piece the reader will (a) understand the importance of health professionals’ ad-vocacy; (b) know how to use policy papers to advocate; and (c) understand how policy organizations use policy papers. We also discuss the National Academies of Medicine, Science, & Engineering High Quality Primary Care report as an example of a policy pa-per, introduce our new coeditors for the Policy and Management Department, and describe the Collaborative Family Health Care Association’s new policy principles