DKTK - Research Program "Molecular Diagnostics, Early Detection and Biomarker Development (MDEB)"

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DKTK - German Consortium for Translational Cancer Research

The DKTK Program Molecular Diagnostics, Early Detection and Biomarker Development is dedicated to the discovery of novel diagnostic, prognostic and predictive molecular markers, the development of approaches for cancer prevention, and the translation of these findings into robust biomarkers to improve the clinical management of cancer patients.

Genetic heterogeneity between tumors and within a tumor is one of the main mechanisms for tumor progression and therapy resistance. To visualize heterogeneity within patients, a detailed analysis of 27 colorectal cancer patients with more than 90 tumor samples was performed. Using targeted sequencing, the 100 most frequently mutated genes in CRC were analyzed for small nuclear variations (SNVs) in conjunction with copy number alterations (CNVs). Only minimal differences were detected between primary tumors and their matched metastases in terms of SNVs, even when several years and therapies were in between the samples. In contrast, copy number alterations showed strong differences, which occurred to be different between each of the samples. An individual tumor samples was disassembled into 68 individual parts; all parts were analyzed individually and finally the genetic heterogeneity was reconstructed in a 3-dimensional manner. The analysis showed that CNVs of certain genes and chromosomal regions are variable between certain tumor areas. This indicated that genetic heterogeneity is evident not only between different tumor samples, but also within a tumor sample and has to be considered in the future for precise diagnostics (Mamlouk et al. 2017 - link).


The three-dimensional tumor model shows in which areas the copy number of the gene BRCA2 is changed in the CRC tumor. The researchers found a high gene copy number in the inner tumor area (dark red), while the copy number in some outer areas was barely increased (light red) or remained unchanged (white).
© Christine Sers, Soulafa Mamlouk / Charité Berlin

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