Molecular pathology of thymomas: implications for diagnosis and therapy

Abstract

Thymomas exhibit a unique genomic landscape, comprising the lowest on average total mutational burden among adult human cancers; a unique point mutation in the GTF2I gene in WHO type A and AB thymomas (and rarely others); almost unique KMT2A-MAML2 translocations in rare WHO type B2 and B3 thymomas; a unique YAP1-MAML2 translocation in almost all metaplastic thymomas; and unique miRNA profiles in relation to GTF2I mutational status and WHO histotypes. While most thymomas can be diagnosed solely on the basis of morphological features, mutational analyses can solve challenging differential diagnostic problems. No molecular biomarkers have been identified that predict the response of unresectable thymomas to chemotherapy or agents with known molecular targets. Despite the common and strong expression of PDL1 in thymomas, immune checkpoint inhibitors are rarely applicable due to the poor predictability of common, life-threatening autoimmune side effects that are related to the unrivaled propensity of thymomas towards autoimmunity.

Metabolic Profiling of Thymic Epithelial Tumors Hints to a Strong Warburg Effect, Glutaminolysis and Precarious Redox Homeostasis as Potential Therapeutic Targets

“…Due to the differential expression of metabolites in TETs versus normal thymi (Figure 1), pathways related to proline, cysteine, glutathione, lactate and glutamine appear as potential therapeutic targets in refractory TETs, in which targeted treatments have remained elusive [71].…”

Mediastinale Tumore

“…Selbst bei beträchtlicher Größe können Thymome symptomfrei bleiben. Tumorbiologisch bestehen 2 seltene und wichtige Charakteristika: die einmalige Häufigkeit von fast 50 % paraneoplastischer Autoimmunphänomene und die Art der Metastasierung mit der Neigung von B2-und B3-Thymomen zu pleuraler Aussaat[30,31,32].…”

Molecular profiling of rare thymoma using next-generation sequencing: meta-analysis

“…A recent study has demonstrated common loss-of-function in TP53 in type B thymomas and TCs. 30 In a study by Peric et al ., two variants with stop codon have been identified R213* and V91*, as well as four pathogenic missense changes namely, D281N, G244S, R158C, E221K. 22 , 31 , 32 One of the newest studies by Xu S et al ., included in our meta-analysis, has analyzed the genomic profile of TETs that has indicated TP53 as the most mutated gene especially in both B3 and C thymoma causing worse prognosis.…”