Germline Mutations in Cancer Predisposition Genes are Frequent in Sporadic Sarcomas.

Associations of sarcoma with inherited cancer syndromes implicate genetic predisposition in sarcoma development. However, due to the apparently sporadic nature of sarcomas, little attention has been paid to the role genetic susceptibility in sporadic sarcoma. To address this, we performed targeted-genomic sequencing to investigate the prevalence of germline mutations in known cancer-associated genes within an Asian cohort of sporadic sarcoma patients younger than 50 years old. We observed 13.6% (n = 9) amongst 66 patients harbour at least one predicted pathogenic germline mutation in 10 cancer-associated genes including ATM, BRCA2, ERCC4, FANCC, FANCE, FANCI, MSH6, POLE, SDHA and TP53. The most frequently affected genes are involved in the DNA damage repair pathway, with a germline mutation prevalence of 10.6%. Our findings suggests that genetic predisposition plays a larger role than expected in our Asian cohort of sporadic sarcoma, therefore clinicians should be aware of the possibility that young sarcoma patients may be carriers of inherited mutations in cancer genes and should be considered for genetic testing, regardless of family history. The prevalence of germline mutations in DNA damage repair genes imply that therapeutic strategies exploiting the vulnerabilities resulting from impaired DNA repair may be promising areas for translational research.

Effect of postoperative radiation therapy on mandibular reconstruction using a modular endoprosthesis - a pilot study.

The endoprosthetic system has been shown to be a potential option for mandibular reconstruction. The objective of this pilot in vivo animal study was to determine the effects of postoperative radiation using brachytherapy on bone and soft tissue healing in mandibles reconstructed with the endoprosthesis. Six adult Macaca fascicularis mandibles were reconstructed with a cemented endoprosthesis after segmental body resection. The animals were divided into two groups. The test group was subjected to radiation therapy 1 month postoperation while the control group did not receive any radiation. Results showed no major radiation side effects. Mucosal ulcerations and wound dehiscence at the radiated sites healed within 4 weeks. One animal from each group had prosthesis failure and was unable to complete the study. Micro-CT findings indicated no significant differences between the total bone volume percentage (TBV%) of the study and control groups. Histomorphometrical analysis using grading scales also showed no significant differences between the two groups. Under the study conditions, postoperative brachytherapy did not affect the tissue response around the endoprosthesis within the early 6 months postradiation period. The endoprosthesis, therefore, remains a viable reconstructive option when postoperative radiation is prescribed.