Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine

Radius Scanning Parameters

Scanning parameters for the radius to be used in conjunction with CT reconstructive softwar

Radius JPEG Stack

Ulna JPEG stacks representing individual CT slices

First diagnosis of septic arthritis in a dinosaur

Identification and interpretation of pathologies in the fossil record allows for unique insights into the life histories of extinct organisms. However, the rarity of such finds limits not only the sample size for palaeopathologic studies, but also the types of analyses that may be performed. In this study, we present the first occurrence of a palaeopathology in a vertebrate from the Mesozoic of the East Coast of North America (Appalachia), a pathologic ulna and radius of an indeterminate hadrosaur from the Navesink Formation (New Jersey). X-ray microtomography allowed for both detailed and more accurate diagnosis of the pathologic condition as well as virtual conservation of the specimen. Based on extant archosaurian comparisons, the hadrosaur was diagnosed with severe septic arthritis affecting the proximal ulna and radius. Diagnosis was based on erosion of the joint and highly reactive periosteal bone growth and fusion of the elements. To the best of our knowledge, this is the first recorded account of septic arthritis in dinosaurs. The severity of the pathology suggests the animal suffered with this condition for some time before death. Unfortunately, only the ulna and radius were found. Thus, the extent to which the condition spread to other parts of the body is unknown

Data from: First diagnosis of septic arthritis in a dinosaur

Identification and interpretation of pathologies in the fossil record allows for unique insights into the life histories of extinct organisms. However, the rarity of such finds limits not only the sample size for palaeopathologic studies, but also the types of analyses that may be performed. In this study, we present the first occurrence of a palaeopathology in a vertebrate from the Mesozoic of the East Coast of North America (Appalachia), a pathologic ulna and radius of an indeterminate hadrosaur from the Navesink Formation (New Jersey). X-ray microtomography allowed for both detailed and more accurate diagnosis of the pathologic condition as well as virtual conservation of the specimen. Based on extant archosaurian comparisons, the hadrosaur was diagnosed with severe septic arthritis affecting the proximal ulna and radius. Diagnosis was based on erosion of the joint and highly reactive periosteal bone growth and fusion of the elements. To the best of our knowledge, this is the first recorded account of septic arthritis in dinosaurs. The severity of the pathology suggests the animal suffered with this condition for some time before death. Unfortunately, only the ulna and radius were found. Thus, the extent to which the condition spread to other parts of the body is unknown

Radius VGL file

Can be opened with vgsutiomax for reconstruction of the radius

Ulna MCS file

Ulna file that can be opened in using the mimics software. Can use to scroll through individual slices

Ulna JPEG Stack

Ulna JPEG stacks representing individual CT slices

Radius MCS file

Radius file that can be opened in using the mimics software. Can use to scroll through individual slices