RESUMO
Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, we report human papillomavirus features and genomic landscape in SCCC via high-throughput HPV captured sequencing, whole-genome sequencing, whole-transcriptome sequencing, and OncoScan microarrays. HPV18 infections and integrations are commonly detected. Besides MYC family genes (37.9%), we identify SOX (8.4%), NR4A (6.3%), ANKRD (7.4%), and CEA (3.2%) family genes as HPV-integrated hotspots. We construct the genomic local haplotype around HPV-integrated sites, and find tandem duplications and amplified HPV long control regions (LCR). We propose three prominent HPV integration patterns: duplicating oncogenes (MYCN, MYC, and NR4A2), forming fusions (FGFR3-TACC3 and ANKRD12-NDUFV2), and activating genes (MYC) via the cis-regulations of viral LCRs. Moreover, focal CNA amplification peaks harbor canonical cancer genes including the HPV-integrated hotspots within MYC family, SOX2, and others. Our findings may provide potential molecular criteria for the accurate diagnosis and efficacious therapies for this lethal disease.
Assuntos
Alphapapillomavirus , Carcinoma de Células Pequenas , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Proteínas Associadas aos Microtúbulos/genética , Proteína Proto-Oncogênica N-Myc/genética , Proteínas Nucleares/genética , Papillomaviridae/genética , Neoplasias do Colo do Útero/patologia , Integração Viral/genéticaRESUMO
ObjectiveTo investigate the clinical features of postpartum hemolytic uremic syndrome (PHUS) in Tibetan women, and to improve the diagnosis and treatment of PHUS.MethodsFrom January 2013 to June 2018, 11 patients diagnosed with PHUS in the Tibet Autonomous Regional People's Hospital were enrolled. Clinical manifestations, laboratory testing results, treatments and outcomes were retrospectively analyzed. A descriptive statistical analysis was applied in this study.ResultsThe average age of the 11 patients was (27.0±6.2) years old, and all were Tibetans. Five of them delivered by cesarean section and eight complicated by hypertension. The onset of PHUS was 1-3 d after delivery. The mean hemoglobin concentration [(73.5±26.3) g/L] and platelet count [(51±31)×109/L] remarkably decreased. Patients' renal functions were also significantly impaired with an average serum creatinine level of (517±184)μmol/L. Nine women required hemodialysis, seven received plasma infusion and six underwent glucocorticoid therapy. No patients received plasma exchange or eculizumab therapy due to limited resources. Seven out of the nine patients who underwent hemodialysis could withdraw from dialysis.ConclusionsPHUS is relatively rare, and characterized by acute onset after birth and severe conditions, especially renal injury. However, most patients would have better prognosis after active treatment.
