RESUMEN
BACKGROUND: Viruses and other infectious agents cause more than 15% of human cancer cases. High-throughput sequencing-based studies of virus-cancer associations have mainly focused on cancer transcriptome data. METHODS: In this study, we applied a diverse selection of presequencing enrichment methods targeting all major viral groups, to characterize the viruses present in 197 samples from 18 sample types of cancerous origin. Using high-throughput sequencing, we generated 710 datasets constituting 57 billion sequencing reads. RESULTS: Detailed in silico investigation of the viral content, including exclusion of viral artefacts, from de novo assembled contigs and individual sequencing reads yielded a map of the viruses detected. Our data reveal a virome dominated by papillomaviruses, anelloviruses, herpesviruses, and parvoviruses. More than half of the included samples contained 1 or more viruses; however, no link between specific viruses and cancer types were found. CONCLUSIONS: Our study sheds light on viral presence in cancers and provides highly relevant virome data for future reference.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Metagenoma/genética , Neoplasias/virología , Anelloviridae/genética , Anelloviridae/aislamiento & purificación , Biopsia , Conjuntos de Datos como Asunto , Femenino , Herpesviridae/genética , Herpesviridae/aislamiento & purificación , Humanos , Masculino , Neoplasias/patología , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Parvovirus/genética , Parvovirus/aislamiento & purificaciónRESUMEN
Although nearly one fifth of all human cancers have an infectious aetiology, the causes for the majority of cancers remain unexplained. Despite the enormous data output from high-throughput shotgun sequencing, viral DNA in a clinical sample typically constitutes a proportion of host DNA that is too small to be detected. Sequence variation among virus genomes complicates application of sequence-specific, and highly sensitive, PCR methods. Therefore, we aimed to develop and characterize a method that permits sensitive detection of sequences despite considerable variation. We demonstrate that our low-stringency in-solution hybridization method enables detection of <100 viral copies. Furthermore, distantly related proviral sequences may be enriched by orders of magnitude, enabling discovery of hitherto unknown viral sequences by high-throughput sequencing. The sensitivity was sufficient to detect retroviral sequences in clinical samples. We used this method to conduct an investigation for novel retrovirus in samples from three cancer types. In accordance with recent studies our investigation revealed no retroviral infections in human B-cell lymphoma cells, cutaneous T-cell lymphoma or colorectal cancer biopsies. Nonetheless, our generally applicable method makes sensitive detection possible and permits sequencing of distantly related sequences from complex material.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neoplasias/virología , Retroviridae/genética , Animales , Secuencia de Bases , Sondas de ADN/metabolismo , ADN Viral/genética , Biblioteca de Genes , Genoma Humano , Células HEK293 , VIH-1/genética , Humanos , Provirus/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Sus scrofaRESUMEN
A 25-year-old female nurse was referred to our diabetes outpatient clinic with poorly controlled type 2 diabetes, obesity and elevated liver function tests (LFTs). Following a liver biopsy she was diagnosed with non-alcoholic steatohepatitis (NASH) and liver fibrosis. Treatment with subcutaneous injections of the glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide was initiated. After 46 weeks of treatment the patient had lost 16 kg, glycemic control was excellent and LFTs had normalized. Repeat liver biopsy and ultrasound showed reduction in hepatic fat content and inflammatory cells. The biopsy no longer fulfilled the criteria for NASH. The liver biopsies did not express hepatic GLP-1Rs using quantitative polymerase chain reaction. Our case suggests that liraglutide may benefit patients with NASH.
RESUMEN
Epithelioid trophoblastic tumour is a rare gestational trophoblastic disease. The diagnosis is based on microscopic morphology and immunohistochemical staining. It is important to avoid misdiagnosis, as this tumour is primarily treated by surgery rather than chemotherapy. We report a case and describe diagnostic criteria and differential diagnoses.