Archiv Juni 2011

Tumorzellen haben weniger Chancen - dem Restrisiko auf der Spur

Hochsensitive Verfahren zum direkten Nachweis von Tumorzellen und tumorzellspezifischen Veränderungen auf der Ebene des Erbmaterials erhalten zunehmend Einzug in die klinische Praxis. Aktuell sind zytologische und molekulargenetische Verfahren wichtige diagnostische Bausteine im Rahmen der Untersuchung auf das Vorliegen einer minimalen Resterkrankungen hämatologischer Malignome, vor allem der akuten lymphatischen Leukämie (ALL) geworden. Mit diesen Methoden können geringste Mengen Tumorzellen in Knochenmark, peripherem Blut oder auch anderen Geweben bzw. Körperkompartimenten (z.B. Lymphknoten, Metastasen, Liquor, Urin etc.) nachgewiesen werden.

Detection of human tumor cells by amplicon fusion site polymerase chain reaction (AFS-PCR).

Weber A, Taube S, Starke S, Bergmann E, Christiansen NM, Christiansen H.

J Clin Invest. 2011 Feb 1;121(2):545-53.

Reliable diagnostic strategies for individuals with cancer demand practical methods for highly sensitive and specific detection of tumor cells. Amplification of genomic regions that include putative oncogenes is common in tumor cells of various types. Genomic array platforms offer the opportunity to identify and precisely map amplified genomic regions (ampGRs). The stable existence of these tumor cell-specific genomic aberrations during and after therapy, in theory, make ampGRs optimal targets for cancer diagnostics. In this study, we mapped ampGRs around the proto-oncogene MYCN of human neuroblastomas using a high-resolution tiling array (HR-TA). Based on the HR-TA data, we were able to precisely describe the telomeric and centromeric borders of the ampGRs and deduce virtual fusion sites of the joined ampGRs (amplicon fusion sites [AFSs]). These AFSs served as blueprints for the subsequent design of AFS bridging PCR assays (AFS-PCRs). Strikingly, these assays were absolutely tumor cell specific and capable of detecting 1 tumor cell in 1 × 106 to 8 × 106 control cells. We successfully proved the in vivo practicability of AFS-PCR by detecting and quantifying the specific AFS DNA of human MYCN-amplified neuroblastomas in the patients' corresponding peripheral blood and bone marrow samples. Thus, we believe AFS-PCR could become a powerful and nevertheless feasible personalized diagnostic tool applicable to a large number of cancer patients, including children with MYCN-amplified neuroblastomas.

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