For centuries, entire male pigs have been castrated to reduce the risk of boar taint. However, physical castration of pig is increasingly being questioned with regard to animal welfare considerations. Immunization against gonadotrophin releasing hormone (GnRH) provides an alternative to physical castration. Using the currently available commercial product (Improvac R ; Pfizer Animal Health), a two-dose regimen of a GnRH vaccine is administered. After the second vaccination, a substantial increase in feed consumption has been reported, which may be associated with increased body fatness and decreased feed efficiency when compared with unvaccinated entire male pigs. The aim of the present study was to investigate the effect of a feed restriction on these traits and on the behaviour of 120 group-housed entire males (five pigs/pen) vaccinated against GnRH. The first vaccination was performed at 62 days of age and the second (V2) at 130 days of age. Pigs were slaughtered in two batches 4 to 5 weeks after V2. They were either offered feed ad libitum over the 22 to 114 kg BW range (AL treatment) or ad libitum up to a maximum of 2.50 (R2.50 treatment) or 2.75 kg/day per pig (R2.75 treatment). Behavioural observations and skin lesion scoring were conducted 1 week before V2, and 1 and 3 weeks after V2. At slaughter, the volumetric lean meat content was measured using an X-ray computed tomography scanner. Between V2 and slaughter, the average feed intakes for the R2.75 and R2.50 treatments were 15% and 22% lower than the average AL feed intake (3.20 kg/day), respectively. Feed restriction was associated with a reduced average daily gain after V2 (846, 932 and 1061 g/day in the R2.50, R2.75 and AL groups, P , 0.01) but had no effect on the feed conversion ratio (3.00 kg feed/kg BW gain on average, P 5 0.62). No difference was observed in the lean meat content (71.8%, 70.7% and 70.4% in the R2.50, R2.75 and AL groups, P 5 0.14), despite a reduced backfat thickness measured in restrictively fed pigs (12.0, 13.0 and 13.6 mm in the R2.50, R2.75 and AL groups, P , 0.01). Higher skin lesion scores were observed 3 weeks after V2 in R2.50 and R2.75 pigs than in the AL ones (scores 33.4, 27.7 and 25.5, respectively, P 5 0.04). These results, combined with an unimproved feed efficiency and no marked change in carcass characteristics, suggest that immunologically castrated pigs should not be restrictively fed during the late finishing period.

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Based on the transcriptome analysis of 555 sarcomas, we identified a group of tightly clustered leiomyosarcomas (LMS) due to their gene expression homogeneity. We named them "hLMS" and the other LMS "oLMS". We derived a transcriptional signature able to identify each group and used it to classify patients from two independent cohorts. In all cohorts, hLMS were preferentially carried by women, located in the internal trunk, highly differentiated, and similarly altered at the genomic level. Based on integrative bioinformatic analysis, we show that hLMS originate from vascular smooth muscle cells presenting both contractile and synthetic characteristics, while oLMS could derive from fibroblasts. We found strong MYOCD expression to be an hLMS-specific driver and show that the MYOCD/SRF axis is essential only for hLMS survival. Identification of hLMS could become standard clinical practice, leading to the development of specific effective treatments with MYOCD/SRF inhibitors.

Leiomyosarcoma (LMS) is an aggressive smooth muscle cancer with few therapeutic options. LMSs show a high level of genomic instability (GI) and the mechanisms underlying their oncogenic processes are poorly understood. While the level of GI influences treatment efficacy and resistance, an accurate measure of it is lacking. Current measures of GI are based on counts of specific structural variation (SV) and mutational signatures. Here, we present a holistic approach to measuring GI based on the quantification of the steady-state equilibrium between DNA damage and repair as assessed by the residual breakpoints (BP) remaining after repair, irrespective of SV type. We use the notion of Hscore, a BP “hotspotness” magnitude scale, to measure the propensity of genomic structural or functional DNA elements to break more than expected by chance. We then derived new measures of transcription- and replication-associated GI that we call iTRAC (Transcription-Associated Chromosomal instability index (iTRAC) and iRACIN (Replication-Associated Chromosomal INstability index). We show that iTRAC and iRACIN are predictive of metastatic relapse in LMS and that they may be combined to form a new classifier called MAGIC (Mixed transcription-and replication-Associated Genomic Instability Classifier). MAGIC outperforms the gold standards FNCLCC and CINSARC in stratifying metastatic risk in LMS. Furthermore, iTRAC stratifies chemotherapeutic response in LMS. We finally show that this approach is applicable to other cancers.