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Intracranial germ cell tumours (IGCTs) are a group of rare heterogeneous brain tumours that are clinically and histologically similar to the more common gonadal GCTs. IGCTs show great variation in their geographical and gender distribution, histological composition and treatment outcomes. The incidence of IGCTs is historically five- to eightfold greater in Japan and other East Asian countries than in Western countries, with peak incidence near the time of puberty. About half of the tumours are located in the pineal region. The male-to-female incidence ratio is approximately 3-4:1 overall, but is even higher for tumours located in the pineal region. Owing to the scarcity of tumour specimens available for research, little is currently known about this rare disease. Here we report the analysis of 62 cases by next-generation sequencing, single nucleotide polymorphism array and expression array. We find the KIT/RAS signalling pathway frequently mutated in more than 50% of IGCTs, including novel recurrent somatic mutations in KIT, its downstream mediators KRAS and NRAS, and its negative regulator CBL. Novel somatic alterations in the AKT/mTOR pathway included copy number gains of the AKT1 locus at 14q32.33 in 19% of patients, with corresponding upregulation of AKT1 expression. We identified loss-of-function mutations in BCORL1, a transcriptional co-repressor and tumour suppressor. We report significant enrichment of novel and rare germline variants in JMJD1C, which codes for a histone demethylase and is a coactivator of the androgen receptor, among Japanese IGCT patients. This study establishes a molecular foundation for understanding the biology of IGCTs and suggests potentially promising therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway.

Background: Childhood CNS primitive neuro-ectodermal brain tumours (PNETs) are very aggressive brain tumours for which the molecular features and best treatment approaches are unknown. We assessed a large cohort of these rare tumours to identify molecular markers to enhance clinical management of this disease., Methods: We obtained 142 primary hemispheric CNS PNET samples from 20 institutions in nine countries and examined transcriptional profiles for a subset of 51 samples and copy number profiles for a subset of 77 samples. We used clustering, gene, and pathway enrichment analyses to identify tumour subgroups and group-specific molecular markers, and applied immunohistochemical and gene-expression analyses to validate and assess the clinical significance of the subgroup markers., Findings: We identified three molecular subgroups of CNS PNETs that were distinguished by primitive neural (group 1), oligoneural (group 2), and mesenchymal lineage (group 3) gene-expression signatures with differential expression of cell-lineage markers LIN28 and OLIG2. Patients with group 1 tumours were most often female (male:female ratio 0·61 for group 1 vs 1·25 for group 2 and 1·63 for group 3; p=0·043 [group 1 vs groups 2 and 3]), youngest (median age at diagnosis 2·9 years [95% CI 2·4-5·2] for group 1 vs 7·9 years [6·0-9·7] for group 2 and 5·9 years [4·9-7·8] for group 3; p=0·005), and had poorest survival (median survival 0·8 years [95% CI 0·5-1·2] in group 1, 1·8 years [1·4-2·3] in group 2 and 4·3 years [0·8-7·8] in group 3; p=0·019). Patients with group 3 tumours had the highest incidence of metastases at diagnosis (no distant metastasis:metastasis ratio 0·90 for group 3 vs 2·80 for group 1 and 5·67 for group 2; p=0·037)., Interpretation: LIN28 and OLIG2 are promising diagnostic and prognostic molecular markers for CNS PNET that warrant further assessment in prospective clinical trials., Funding: Canadian Institute of Health Research, Brainchild/SickKids Foundation, and the Samantha Dickson Brain Tumour Trust., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Cosmetic surgery is increasingly popular globally, but how cosmetic surgery patients are socially evaluated is largely unknown. The present research documents attitudes toward these patients in multiple cultures (Hong Kong, Japan, and the United States). Across these cultures, attitudes toward cosmetic surgery patients were predominantly negative: Participants ascribed more negative attributes to cosmetic surgery patients and found cosmetic surgery not acceptable. Also, participants in Hong Kong and Japan were not willing to form social relationships, particularly intimate ones, with these patients. These attitudes were less negative in the United States than in Hong Kong and Japan, partly because social contact, which reduced negativity in attitudes toward cosmetic surgery patients, was more prevalent in the United States. These findings bear important implications for the subjective well-being of cosmetic surgery patients, who very often expect improvement in their social relationships through the surgery.

The epsilon4 allele of apolipoprotein E (ApoE) is a risk factor in late-onset Alzheimer's disease (AD). As a receptor for ApoE, very-low-density lipoprotein receptor (VLDLR) might be involved in AD pathogenesis. A Japanese study [Okuizimi, K., et al., Nature Genet., 11 (1995) 207-209] has shown an increased 5 and decreased 8 CGG-repeat allele frequency in the 5' untranslated region of VLDLR in Japanese AD versus normal controls (N). Subsequent studies in Caucasian Americans failed to duplicate the result. We examined this polymorphism in pathologically- or clinically-diagnosed Chinese late-onset AD. Our data did not show a significant increase in the 5 CGG-repeat in AD, thus suggesting no association to VLDLR. However, our data did show that the allele frequencies for each CGG-repeat were similar in both Chinese and Japanese.