RESUMEN
The utility of cancer whole genome and transcriptome sequencing (cWGTS) in oncology is increasingly recognized. However, implementation of cWGTS is challenged by the need to deliver results within clinically relevant timeframes, concerns about assay sensitivity, reporting and prioritization of findings. In a prospective research study we develop a workflow that reports comprehensive cWGTS results in 9 days. Comparison of cWGTS to diagnostic panel assays demonstrates the potential of cWGTS to capture all clinically reported mutations with comparable sensitivity in a single workflow. Benchmarking identifies a minimum of 80× as optimal depth for clinical WGS sequencing. Integration of germline, somatic DNA and RNA-seq data enable data-driven variant prioritization and reporting, with oncogenic findings reported in 54% more patients than standard of care. These results establish key technical considerations for the implementation of cWGTS as an integrated test in clinical oncology.
Asunto(s)
Perfilación de la Expresión Génica , Neoplasias , Niño , Estudios de Factibilidad , Perfilación de la Expresión Génica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Estudios Prospectivos , Transcriptoma/genética , Secuenciación Completa del Genoma/métodos , Adulto JovenRESUMEN
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. Rhabdomyosarcoma, the most common soft tissue sarcoma of childhood. makes up less than 1% of solid malignancies in adults with around 400 new cases each year in the United States. They have not previously been reported concurrently. CASE PRESENTATION: A 37 year old woman presented with painful enlarging leg mass. Biopsy of the mass was consistent with embryonal rhabdomyosarcoma. Staging imaging revealed a PET avid anterior mediastinal lymph node. Excisional biopsy of this mass was consistent with diffuse large B-cell lymphoma. Hybridization capture-based next-generation DNA sequencing did not reveal shared somatic tumor mutations. Germline analysis did not show identifiable aberrations of TP53 or other heritable cancer susceptibility genes. She was treated with a personalized chemotherapy regimen combining features of R-CHOP and Children's Oncology Group ARST 0331. CONCLUSIONS: This case illustrates a unique clinical entity successfully treated with a personalized chemotherapeutic regimen.
RESUMEN
An asymptomatic renal oncocytoma was found in the upper left quadrant of an eighty-five-year-old woman during a routine physical examination. Ultrastructurally, the tumor was composed entirely of epithelial cells filled with normal and abnormal mitochondria. Selective renal angiography showed two renal arteries supplying a lobulated, highly vascular mass. The mass contained irregular and tortuous vessels without any arteriovenous shunting.
Asunto(s)
Adenoma/patología , Neoplasias Renales/patología , Adenoma/irrigación sanguínea , Adenoma/ultraestructura , Anciano , Angiografía , Femenino , Humanos , Neoplasias Renales/irrigación sanguínea , Neoplasias Renales/ultraestructura , Arteria Renal/diagnóstico por imagenRESUMEN
This paper attempts to outline a model for the evaluation of a statewide mental health program drawn from general systems theory. The derived model is partially stated and illustrative applications discussed. Inferential procedures as applied to evaluation research are discussed and experimental inference is stated to be inapplicable to most evaluation problems. Evaluative technique is applied not only to the attainment of ultimate objectives but to the attainment of intermediate objectives as well. In this latter connection, there is a brief discussion of program budgeting and its relation to evaluation studies.