Genetic Profiling in Soft Tissue Sarcoma

摘要: Soft tissue sarcomas (STS) are a heterogeneous group of highly malignant mesenchymal tumors that account for ~1% all malignancies. Frequent heterogeneity and pleomorphism along with suboptimal diagnostic reproducibility insufficient prognostic markers make clinical management these difficult. This thesis has applied microarray-based gene expression copy-number profiling to STS. The studies provide clues the genetic pathways involved in STS development identify profiles linked diagnosis prognosis. results from Study I concerns intratumor versus intertumor fibrous histiocytoma (MFH) leiomyosarcoma (LMS), suggest may be particularly relevant small tumor series thus serve as reminder run larger sample sets increased reliability. II established patterns related SS18-SSX fusion variants metastatic potential synovial sarcoma (SS). differential various developmental genes, transcription factors, histones, metallothioneins suggests have distinct downstream effects. In III, 177 mixed histopathological subtypes were profiled using cDNA microarrays. Distinct identified specific translocations or mutations. Herein, frequent upregulation e.g. Wingless Hedgehog signaling pathways, was demonstrated. more pleomorphic showed overexpression genes proliferation, adhesion, motility protein degradation. Moreover, signature partly characterized by hypoxia-related within IV array-based comparative genomic hybridization MFH LMS, demonstrated extensive complexity multiple recurrent gains losses, novel amplifications homozygous deletions. Losses chromosomal regions 6q14 7q36 provided information independent previously risk factors. summary, demonstrate herein, define heterogeneity, SS yield different effects, subsets STS, tumors, discern prognostically important alterations plethora aberrations characterize many (Less)