Cancer Research

The focal area of cancer research covers a wide range of different topics: from basic science research questions mostly addressed by molecular biologists to the development of novel assays for routine diagnostics in cooperation with pathologists. The daily interplay of biologists and pathologists, as well as the close proximity and strong collaboration with the department of oncology, represent a unique translational cancer research environment. Further, our institute is well known for its expertise in the detection of novel prognostic and predictive markers for neoplastic diseases. To a large extent, this work was achieved by the use of tissue microarrays (TMA) and has resulted in numerous scientific publications. Our research groups focus on different questions, but all of them contribute with their research to a better understanding of tumorigenesis and aim at providing better tools for cancer diagnostics and treatment. Below, two representative topics of this focal area are summarized.

1. Understanding the genomic mechanisms responsible for tumorigenesis, clonal evolution and therapy resistance

It is well known that cancer is caused and driven by an accumulation of genomic aberrations and mutations. Different research groups of our institute take advantage of the latest novel sequencing technologies as well as on the availability of unique patient cohorts in order to detect and define genes and pathways involved in tumor progression and therapy resistance. We perform these analyses in hematological neoplastic malignancies (such as DLCBCL), as well as in osteosarcomas and in carcinomas from the skin (malignant melanoma), the lung (NSCLC), the bladder, the prostate and the liver (HCC). For assessing the clonal architecture of these tumors, we apply mathematical modelling or fluorescence-based activated cell sorting.

Recent publications (selected):

  • Juskevicius et al., Distinct genetic evolution patterns of relapsing diffuse large B-cell lymphoma revealed by genome wide copy number aberration and targeted sequencing analysis. Leukemia, 2016.
  • Kovac et al., Exome sequencing of osteosarcoma reveals mutation signatures reminiscent of BRCA deficiency. Nat Commun 2015.
  • Ribi et al., TP53 intron 1 hotspot rearrangements are specific to sporadic osteosarcoma and can cause Li-Fraumeni syndrome. Oncotarget 2015.
  • Brunner et al., Follicular lymphoma transformation into histiocytic sarcoma: indications for a common neoplastic progenitor. Leukemia 2014.
  • Ruiz et al., Advancing a clinically relevant perspective of the clonal nature of cancer. PNAS, 2011.
  • Smida et al., Genomic alterations and allelic imbalances are strong prognostic predictors in osteosarcoma. Clin Cancer Res, 2010.

2. The use of liquid biopsies for monitoring cancer patients

Circulating tumor cells (CTCs) and circulating cell-free DNA (cfDNA) originate from the tumor and can be detected in the blood of patients with advanced neoplastic disease. Novel technologies, such as next-generation sequencing (NGS) and digital PCR allow for an efficient and highly sensitive analysis of this DNA. These analyses can be used for monitoring the patients’ tumor burden as well as detecting resistant mutations that may arise under therapy. In different studies in collaboration with different clinical departments, we assess the usefulness of these liquid biopsies as a minimal invasive biopsy system for monitoring patients’ therapy response.

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