Malignant germ cell tumours of childhood: new associations of genomic imbalance

Malignant germ cell tumours (MGCTs) of childhood are a rare group of neoplasms that comprise many histological subtypes and arise at numerous different sites. Genomic imbalances have been described in these tumours but, largely because of the paucity of cases reported in the literature, it is unclear how they relate to abnormalities in adult MGCTs and impact on potential systems for classifying GCTs. We have used metaphase-based comparative genomic hybridisation to analyse the largest series of paediatric MGCTs reported to date, representing 34 primary tumours (22 yolk sac tumours (YSTs), 11 germinomatous tumours and one metastatic embryonal carcinoma) occurring in children from birth to age 16, including 17 ovarian MGCTs. The large dataset enabled us to undertake statistical analysis, with the aim of identifying associations worthy of further investigation between patterns of genomic imbalance and clinicopathological parameters. The YSTs showed an increased frequency of 1p- (P=0.003), 3p+ (P=0.02), 4q− (P=0.07) and 6q− (P=0.004) compared to germinomatous tumours. Gain of 12p, which is invariably seen in adult MGCTs, was present in 53% of primary MGCTs of children aged 5–16 and was also observed in four of 14 YSTs affecting children less than 5. Two of these cases (14% of MGCTs in children less than 5) showed gain of the 12p11 locus considered to be particularly relevant in adult MGCTs. Gain of 12p showed a significant association with gain of 12q. Conversely, MGCTs without 12p gain displayed a significantly increased frequency of loss on 16p (P=0.04), suggesting that this imbalance may contribute to tumour development in such cases. This data provides new insight into the biology of this under-investigated tumour group and will direct future studies on the significance of specific genetic abnormalities

Effect of three treatment schedules of recombinant methionyl human leptin on body weight in obese adults: a randomized, placebo-controlled trial

Aim:  The aim of this study was to evaluate the effect on body weight and safety of subcutaneously administered recombinant leptin in obese adults and to evaluate whether the timing of recombinant leptin administration influences efficacy. Methods:  A randomized, double-blind, placebo-controlled, multicentre study was designed, comprising of a 3-week dietary lead-in followed by a 12-week leptin or placebo treatment period. A total of 284 overweight and obese (body mass index 27–37.0 kg/m2) predominantly white (98%) women (66%) and men (34%) with a mean (±s.d.) 46.8 ± 10.4 years of age were randomized into three treatment groups with three matching placebo groups. Recombinant leptin was administered by subcutaneous injection [10 mg/morning, 10 mg/evening or 20 mg/day (10 mg twice daily)]. Patients were counselled at baseline to reduce dietary intake by 2100 kJ/day (500 kcal/day), and dietary advice was reinforced every 2–4 weeks. Results:  No statistically significant change in body weight occurred with recombinant leptin treatment compared with placebo treatment in any treatment group. No clinically significant adverse effects were observed with the exception of an increase in injection-site reactions in patients treated with recombinant leptin (83%) vs. placebo (36%). Conclusions:  Administration of recombinant leptin to an overweight and obese population, in addition to a mildly energy-restricted diet, was not efficacious in terms of weight loss at the doses and schedules studied. The hypothesis that nocturnal administration of recombinant leptin might have a specific effect on weight loss was not supported