Consistent MYC and FLT4 gene amplification in radiation‐induced angiosarcoma but not in other radiation‐associated atypical vascular lesions

• DOI: 10.1002/gcc.20827
• Publication Date: 2010-10-14T16:42:28Z
• Authors: Tianhua Guo; Lei Zhang; Ning‐En Chang; Samuel Singer; Robert G. Maki; Cristina R Antonescu
• Keywords: Pathogenesis

Abstract Angiosarcoma (AS) is a distinct group of sarcomas characterized by upregulation vascular‐specific receptor tyrosine kinases, including TIE1 , KDR TEK and FLT1. In keeping with the clinical heterogeneity, gene‐expression profiling distinguishes two AS genomic clusters, which correlate anatomical location prior exposure to radiation. Furthermore, high percentage secondary AS, but not primary shows 8q24 chromosomal gains, due MYC amplification. this study, we mined transcriptional output 10 11 better define dichotomy in pathogenesis these subsets. The oncogenic role was investigated further as well radiation‐induced atypical vascular lesions (AVL) other radiation‐associated sarcomas. High‐level amplification found 100% none AVL or Coamplification FLT4 (encoding VEGFR3) identified 25% types. Our findings reinforce subtypes, being an early, necessary event AS. Secondary genetic hits, such gene coamplification mutations, may play tumor progression potential therapeutic targeting. © 2010 Wiley‐Liss, Inc.