Discovery of oncogenic ROS1 missense mutations with sensitivity to tyrosine kinase inhibitors.

ROS1 is the largest receptor tyrosine kinase in the human genome. Rearrangements of the ROS1 gene result in oncogenic ROS1 kinase fusion proteins that are currently the only validated biomarkers for targeted therapy with ROS1 TKIs in patients. While numerous somatic missense mutations in ROS1 exist in the cancer genome, their impact on catalytic activity and pathogenic potential is unknown.

Discovery and functional characterization of the oncogenicity and targetability of a novel gene fusion in pediatric angiosarcoma.

Angiosarcomas are rare, malignant soft tissue tumors in children that arise in a wide range of anatomical locations and have limited targeted therapies available. Here, we report a rare case of a pediatric angiosarcoma (pAS) with Li-Fraumeni syndrome (LFS) expressing a novel gene fusion. Although both and are established proto-oncogenes, our study is the first to describe the mechanistic role of - fusion arising via intrachromosomal rearrangement.

Trends in Weight and Body Mass Index after Spinal Surgery for Degenerative Disease.

Background: Currently, 37% of adults in the United States are obese, and 34% are overweight. Obesity poses a particularly complex challenge in spinal surgery management, whereby risk of adverse surgical outcomes increases with increased body mass index (BMI). When patients are counseled to reduce weight to levels associated with acceptable surgical risks, patients often respond that their spinal problems prohibit the exercise needed to lose the required weight and counter that surgery will allow for increased activity and thereby facilitate weight loss.

Association of Preoperative Hemoglobin A1c and Body Mass Index with Wound Infection Rate in Spinal Surgery.

Background: The deleterious effect of diabetes mellitus on surgical outcomes is well documented for joint replacement surgery. We analyzed the large national US Department of Veterans Affairs (VA) database for patients who had undergone elective spinal surgery.

Methods: We retrospectively searched the VA database and identified 174 520 spine cases.

ROS1-dependent cancers - biology, diagnostics and therapeutics.

The proto-oncogene ROS1 encodes a receptor tyrosine kinase with an unknown physiological role in humans. Somatic chromosomal fusions involving ROS1 produce chimeric oncoproteins that drive a diverse range of cancers in adult and paediatric patients. ROS1-directed tyrosine kinase inhibitors (TKIs) are therapeutically active against these cancers, although only early-generation multikinase inhibitors have been granted regulatory approval, specifically for the treatment of ROS1 fusion-positive non-small-cell lung cancers; histology-agnostic approvals have yet to be granted.

Rare but Recurrent ROS1 Fusions Resulting From Chromosome 6q22 Microdeletions are Targetable Oncogenes in Glioma.

Purpose: Gliomas, a genetically heterogeneous group of primary central nervous system tumors, continue to pose a significant clinical challenge. Discovery of chromosomal rearrangements involving kinase genes has enabled precision therapy, and improved outcomes in several malignancies.

Experimental Design: Positing that similar benefit could be accomplished for patients with brain cancer, we evaluated The Cancer Genome Atlas (TCGA) glioblastoma dataset.

Spinal intradural teratomas: developmental programs gone awry?

Intradural spinal teratomas are rare tumors of the spinal cord that are infrequently encountered in children. Although the mechanistic basis for the formation of these tumors is unclear, several lines of evidence suggest that a dysembryogenic process in the embryo results in their formation. The authors present a case of spinal intradural teratoma in an 18-year-old, previously healthy man and review the literature linking the development of these tumors to defects in neurulation and embryogenesis.