Molecular Pathogenesis and Diagnostic, Prognostic and Predictive Molecular Markers in Sarcoma

Abstract

Sarcomas are infrequent malignant mesenchymal neoplasms characterized by notable morphological and molecular heterogeneity. At present, the diagnosis of sarcoma is based on morphology, immunohistochemistry, and clinicopathological correlation. Molecular studies in the clinical setting provide refinements to morphologic sarcoma classification, and contribute diagnostic information (frequently), prognostic stratification (rarely) and predictive information concerning specific therapies (occasionally). In this review, we summarize the major molecular mechanisms that underlie sarcoma pathogenesis, highlighting molecular alterations that provide diagnostic, prognostic or predictive information. The discussion focuses on representative mesenchymal tumor types, following a pathogenic classification combining cytogenetic / genomic information and molecular biologic features. We will address five major molecular alterations frequent in sarcoma, including 1) the presence of chimeric transcription factors, in vascular tumors; 2) abnormal kinase signaling, in gastrointestinal stromal tumor; 3) epigenetic deregulation, either by oncometabolites, as a result of metabolic enzyme mutations, or as primary events, in chondrosarcoma, chondroblastoma, and other tumor types; 4) deregulated cell survival and proliferation, due to extreme copy number alterations, in dedifferentiated liposarcoma; and 5) extreme genomic instability in conventional osteosarcoma, as a representative example of sarcomas with highly complex karyotype.

Potentials of Long Noncoding RNAs (LncRNAs) in Sarcoma: From Biomarkers to Therapeutic Targets

“…So far, there are no specific molecular diagnostic markers [75]. LncRNAs are verified as important regulators of transcription.…”

“…Some prognostic information may be derived from the loss of tumor suppressor genes, such as p53 [75]. More recently, increasing studies indicate that lncRNAs can be effective prognostic biomarkers in osteosarcoma patients.…”

Role of Next-Generation Sequencing as a Diagnostic Tool for the Evaluation of Bone and Soft-Tissue Tumors

“…myxofibrosarcomas, leiomyosarcomas, and pleomorphic sarcomas) [6] . The molecular classification of herein-described bone and soft-tissue tumors is listed in Table 1 [7] . These two lesions can be a diagnostic challenge on small biopsy specimens.…”

Entitäten der Weichteilsarkome

“…Wie bei jeder Regel gibt es jedoch wichtige Ausnahmen, was man an Entitäten wie dem malignen Rhabdoidtumor oder dem Ewing-Sarkom ablesen kann, die sich klinisch und biologisch hoch aggressiv verhalten. Sarkome mit Genfusionen treten in jüngerem Lebensalter auf als solche mit komplexem Karyotyp [12]. .…”