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Grundlage der personalisierten Onkologie ist ein detailliertes Verstandnis des molekularen Profils einer Krebserkrankung. Dieses Profil ist dynamisch und erfordert wahrend des Krankheitsverlaufs ein kontinuierliches Monitoring. Die Bedeutung von Liquid-Biopsy-Analysen fur die Diagnostik, Therapie und Nachsorge in der padiatrischen Hamatologie und Onkologie wurde untersucht. Ausgewahlte technologische, praklinische und translational-klinische Grundlagenarbeiten werden erortert sowie Expertenempfehlungen dargestellt. Die Analyse von Tumorsurrogaten in „liquid biopsies“ wie Blut, Speichel, Nervenwasser und Urin ist weniger invasiv als eine operativ gewonnene Biopsie und kann wiederholt durchgefuhrt werden. Somit ist eine hohe zeitliche Auflosung der Veranderungen im genetischen Fingerabdruck einer Tumorerkrankung moglich. Erste Studien belegen, dass die „liquid biopsy“ anders als eine lokal gewonnene Biopsie die Gesamtheit der Tumorerkrankung erfassen kann und intratumorale Heterogenitat und (sub)klonale Veranderungen reflektiert. Zellfreie Tumor-DNA wird derzeit in der padiatrischen Onkologie am intensivsten studiert. Weitere Tumorsurrogate in „liquid biopsies“ sind RNA-Molekule, zirkulierende Tumorzellen, extrazellulare Vesikel, Metabolite und Proteine. Der technologische Fortschritt des vergangenen Jahrzehnts erlaubt die Detektion und Charakterisierung des dynamischen Fingerabdrucks einer padiatrischen Krebserkrankung in „liquid biopsies“. Die Bedeutung dieser Analysen fur primare Diagnostik, Erfassung von Krankheitsaktivitat, Therapiefuhrung mit zielgerichteten Therapeutika und Fruherkennung von Rezidiven in der Nachsorge wird derzeit in Begleitprogrammen klinischer Studien des Fachgebiets intensiv untersucht.

The rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 and 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, miscellaneous soft-part tissues, the liver and the central nervous system (Atypical Teratoid Rhabdoid Tumors, ATRT). Both, RTPS1&2 are due to pathogenic variants (PV) in genes encoding constituents of the BAF chromatin remodeling complex, i.e. SMARCB1 (RTPS1) and SMARCA4 (RTPS2). In contrast to other genetic disorders related to PVs in SMARCB1 and SMARCA4 such as Coffin-Siris Syndrome, RTPS1&2 are characterized by a predominance of truncating PVs, terminating transcription thus explaining a specific cancer risk. The penetrance of RTPS1 early in life is high and associated with a poor survival. However, few unaffected carriers may be encountered. Beyond RT, the tumor spectrum may be larger than initially suspected, and cancer surveillance offered to unaffected carriers (siblings or parents) and long-term survivors of RT is still a matter of discussion. RTPS2 exposes female carriers to an ill-defined risk of small cell carcinoma of the ovaries, hypercalcemic type (SCCOHT), which may appear in prepubertal females. RT surveillance protocols for these rare families have not been established. To address unresolved issues in the care of individuals with RTPS and to propose appropriate surveillance guidelines in childhood, the SIOPe Host Genome working group invited pediatric oncologists and geneticists to contribute to an expert meeting. The current manuscript summarizes conclusions of the panel discussion, including consented statements as well as non-evidence-based proposals for validation in the future.

The Li-Fraumeni syndrome (LFS, online Mendelian inheritance in man, OMIM #151623) is considered to be one of the currently known most aggressive cancer predisposition syndromes. The heterogeneous spectrum of tumors is dominated by bone and soft tissue sarcomas, various brain tumors, premenopausal breast cancer and adrenocortical carcinoma (ACC). Even in childhood the cancer risk is very strongly increased and it is not uncommon for people with LFS to develop synchronous and metachronous tumors. Typical histopathological findings and molecular genetic signatures can help towards the diagnosis. Inheritance is autosomal dominant and the penetrance appears to be more variable than previously thought. The prevalence of LFS is approximately 1:5000 with a high interregional variance. The LFS is caused by germline mutations in the TP53 gene coding for the protein p53, an essential cellular transcription factor that initiates antitumor responses to cellular stress, such as DNA damage. In people with LFS, due to the loss of functional p53, the protective mechanism of the cells is weakened resulting in a significantly increased cancer risk. In order to improve the survival of people with LFS, structured tumor early recognition and surveillance strategies are recommended; however, national and international longitudinal observational studies are needed to evaluate the cost-effort-benefit balance. For this reason, the authors have established the LFS cancer predisposition registry in which all patients with LFS and other syndromes predisposing to cancer can be registered. Detailed information can be found at www.cancer-predisposition.org .