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- Eckel-Passow, Jeanette E., et al.
(författare)
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Using germline variants to estimate glioma and subtype risks
- 2019
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 21:4, s. 451-461
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Tidskriftsartikel (refereegranskat)abstract
- Background: Twenty-five single nucleotide polymorphisms (SNPs) are associated with adult diffuse glioma risk. We hypothesized that the inclusion of these 25 SNPs with age at diagnosis and sex could estimate risk of glioma as well as identify glioma subtypes.Methods: Case-control design and multinomial logistic regression were used to develop models to estimate the risk of glioma development while accounting for histologic and molecular subtypes. Case-case design and logistic regression were used to develop models to predict isocitrate dehydrogenase (IDH) mutation status. A total of 1273 glioma cases and 443 controls from Mayo Clinic were used in the discovery set, and 852 glioma cases and 231 controls from UCSF were used in the validation set. All samples were genotyped using a custom Illumina OncoArray.Results: Patients in the highest 5% of the risk score had more than a 14-fold increase in relative risk of developing an IDH mutant glioma. Large differences in lifetime absolute risk were observed at the extremes of the risk score percentile. For both IDH mutant 1p/19q non-codeleted glioma and IDH mutant 1p/19q codeleted glioma, the lifetime risk increased from almost null to 2.3% and almost null to 1.7%, respectively. The SNP-based model that predicted IDH mutation status had a validation concordance index of 0.85.Conclusions: These results suggest that germline genotyping can provide new tools for the initial management of newly discovered brain lesions. Given the low lifetime risk of glioma, risk scores will not be useful for population screening; however, they may be useful in certain clinically defined high-risk groups.
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| 2. |
- Pittock, Sean J, et al.
(författare)
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Amphiphysin autoimmunity : paraneoplastic accompaniments
- 2005
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 58:1, s. 96-107
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Tidskriftsartikel (refereegranskat)abstract
- Amphiphysin-IgG was identified in 71 patients among 120,000 evaluated serologically for paraneoplastic autoantibodies. Clinical information was available for 63 patients. Cancer was detected in 50 (mostly limited), proven histologically in 46, and was imaged intrathoracically in 4 patients (lung, small-cell [27] and non-small cell [1]), breast [16] and melanoma [2]). Neurological accompaniments included (decreasing frequency): neuropathy, encephalopathy, myelopathy, stiff-man phenomena, and cerebellar syndrome. In a case examined neuropathologically, parenchymal T-lymphocyte infiltration (predominantly CD8(+)) was prominent in lower brainstem, spinal cord, and dorsal root ganglion. Coexisting paraneoplastic autoantibodies, identified in 74% of patients, predicted a common neoplasm and indicated other neuronal autoantigen targets that plausibly explained several neurological manifestations; for example, P/Q-type Ca(2+)-channel antibody with Lambert-Eaton syndrome (n = 5), anti-neuronal nuclear antibody type 1 with sensory neuronopathy (n = 7), K(+)-channel antibody with limbic encephalitis (n = 1) or neuromyotonia (n = 1), and collapsin response-mediator protein-5-IgG with optic neuritis (n = 3). Patients with isolated amphiphysin-IgG (n = 19) were more likely to be women (with breast cancer, p < 0.05) and to have myelopathy or stiff-man phenomena (p < 0.01). Overall, a minority of women (39%) and men (12%) had stiff-man phenomena. Only 10% of women (some with lung carcinoma) and 4% of men fulfilled diagnostic criteria for stiff-man syndrome.
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