Faculty Bibliography

Background: Osteosarcoma is one of the most common bone malignancies in the pediatric population, although it affects a wide age range. While pathognomonic genomic alterations have been identified in other pediatric bone and soft tissue tumors such as Ewing sarcoma and synovial sarcoma, no such alterations are seen in osteosarcoma. Epigenetic modifications such as global or specific changes in DNA methylation are gaining recognition as a primary mechanism of oncogenesis in pediatric and adult cancers. Identifying unique epigenetic modifications in tumors lacking known fusions could contribute to both diagnosis and selection of potential therapeutic targets. Methods: Using the Illumina Infinium Human Methylation450 BeadChip Array (450K array) platform, we performed genome-wide DNA methylation analysis on 15 osteosarcomas with tissue meeting criteria for methylation analysis, including formalin-fixed paraffin-embedded, frozen, and fresh tissue obtained from NYU and Memorial Sloan Kettering Cancer Center (mean age = 26 years; range 6-80 years). Comparison was made to 10 Ewing sarcomas and 11 synovial sarcomas in the same pilot cohort. Diagnosis was based on histologic criteria and, where available, absence of a known non-osteosarcoma genomic fusion. Unsupervised hierarchical clustering analysis was performed to classify tumor type and to assess for differentially methylated target regions. Results: Osteosarcomas formed a unique subtype on unsupervised hierarchical clustering analysis of DNA methylation. Of the 15 tumors profiled, molecular testing confirming the absence of a known fusion was previously done on 5, and fusion status did not impact clustering. Pathway analysis through MSig

OBJECTIVE: Examine oral complications 6 months after modern radiation therapy (RT) for head and neck cancer (HNC). METHODS: Prospective multi-center cohort study of HNC patients receiving Intensity-Modulated Radiation Therapy (IMRT) or more advanced RT. Stimulated whole salivary flow, maximal mouth opening, oral mucositis, oral pain, oral health-related quality of life (OH-QOL), and oral hygiene practices, were measured in 372 subjects pre-RT and 216 at 6 months from start of RT. RESULTS: Mean stimulated whole salivary flow declined from 1.09 ml/min to 0.47 ml/min at 6 months (p < 0.0001). Mean maximal mouth opening reduced from 45.58 mm to 42.53 mm at 6 months (p < 0.0001). 8.1% of subjects had some oral mucositis at 6 months, including 3.8% with oral ulceration. Mean overall pain score was unchanged. OH-QOL was reduced at 6 months, with changes related to dry mouth, sticky saliva, swallowing solid foods, and sense of taste (p