Investigating the effect of child maltreatment on early adolescent peer-on-peer sexual aggression: testing a multiple mediator model in a non-incarcerated sample of Danish adolescents

Objective: The aim of the present study was to investigate the relationship between child maltreatment and severe early adolescent peer-on-peer sexual aggression, using a multiple mediator model. Methods: The study comprised 330 male Grade 9 students with a mean age of 14.9 years (SD=0.5). Results: Estimates from the mediation model indicated significant indirect effects of child physical abuse on sexual aggression via peer influence and insecure-hostile masculinity. No significant total effect of child sexual abuse and child neglect on sexual aggression was found. Conclusions: Findings of the present study identify risk factors that are potentially changeable and therefore of value in informing the design of prevention programs aiming at early adolescent peer-on-peer sexual aggression in at-risk youth

Abstract 131: Allelic imbalance analysis of uterine carcinosarcoma: An inquiry into the dual nature of the neoplasm

Abstract Uterine carcinosarcoma (UCS), also known as Malignant Mixed Mullerian Tumor, is a neoplasm of the female genital tract that shows histological features of both carcinoma and sarcoma. Some studies have indicated that UCS arises from sarcomatous differentiation of high-grade carcinoma while others have confirmed a bi-clonal nature of the tumor. Given these differences, further investigation in the origin of this tumor with newer approaches and technologies is warranted. In this study we determined the allelic imbalance (AI) profiles of the two components of UCS and compared the AI events that were shared by, or differed between, them. Samples were obtained from 10 patients diagnosed with UCS and were preserved in formalin fixed paraffin embedded (FFPE) blocks. The two components (carcinoma &amp; sarcoma) were identified and micro-dissected, and whole-genome DNA micro-arrays were applied to the isolated DNA. We then applied a sensitive computational method that combines haplotype information with SNP array data to identify somatic segmental copy number variations and copy-neutral loss of heterozygosity (cnLOH). After we obtained the AI events we filtered small events (&amp;lt;2 MB) to rule out germline duplications. We then obtained events that are common to both components by using a criterion of 80% reciprocal overlap. All such events were classified as a gain, loss or cnLOH. We found that, on an average, 80% of the events found in the carcinoma component are common with the sarcoma component. Conversely, only 64% of events seen in the sarcoma component are found in the carcinoma. This may be in part due to the fact that the sarcoma component usually showed greater number of events and most of these events were larger than the corresponding carcinoma component. Also the sarcoma component showed an increased degree of allelic imbalance than the counterpart. We then looked into particular regions of known tumor suppressor and oncogenes and identified loss in the TP53 gene region (60% of tumors), gains in PIK3CA and PTEN gene regions (40% of tumors), among other events. Our analysis showed that the sarcomatous component shared major portions of the AI profile with the carcinomatous component, but also showed additional events and a greater degree of AI. One explanation for this observation can be that the sarcomatous component retains the AI profile of the carcinomatous component and also gathers additional imbalance. This suggests directionality to the development of UCS: that it arises by sarcomatous differentiation of already existing carcinoma of the uterus. We are pursuing additional assessments of point mutations and expression profiles to complement our existing analyses. Citation Format: Aditya S. Deshpande, Zachary Weber, Raed Sulaiman, Natasha Flier, Cheryl Ageton, Mary Fagerness, Joseph Sulaiman, Gareth E. Davies, David Starks, Luis Rojas-Espaillat, Paul A. Scheet, Erik Ehli. Allelic imbalance analysis of uterine carcinosarcoma: An inquiry into the dual nature of the neoplasm. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 131.</jats:p