Citations

Abstract Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here, we report wide variation in the expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in the majority of ovarian cancer cell lines (three SDs above the mean of normal ovarian surface epithelial cells) and high-grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 5′-TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C-to-A and C-to-G transversion mutations within 5′-TC dinucleotide motifs in early-stage high-grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA "repair" enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability. Cancer Res; 73(24); 7222–31. ©2013 AACR.

AbstractBackgroundHibernomas are rare, benign tumors of brown adipose tissue uncommonly found in the head and neck.MethodsA review of the English‐language literature was conducted for this study. We present a series of 2 laryngeal hibernomas treated with transoral laser microsurgical resection at a tertiary referral center over a period of 18 years.ResultsOnly 2 cases of laryngeal hibernoma have been previously described in the literature. Two additional cases were encountered at our institution. Preoperative imaging demonstrated a well‐circumscribed neoplasm with fat density compatible with lipoma, but internal heterogeneity and vascularity seen in the context of liposarcoma. Transoral laser microsurgical resection was successfully performed in each case.ConclusionDespite unique radiographic features, hibernomas are difficult to distinguish from well‐differentiated liposarcoma and lipoma variants without pathologic correlation. Complete surgical resection is indicated. In our experience, transoral laser microsurgical excision of laryngeal hibernomas is a safe, effective treatment modality with little associated morbidity. © 2013 Wiley Periodicals, Inc. Head Neck 36: E39–E43, 2014

ABSTRACTBackgroundVariants within the leucine‐rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine‐rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late‐onset sporadic disorders like Parkinson's disease.MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine‐rich repeat kinase 2 gene across 23 different sites in 15 countries.ResultsHerein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K‐R1398H‐K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups.ConclusionsEstablishing individual patient‐based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. © 2013 International Parkinson and Movement Disorder Society