More options for patients: Advantages of whole genome/RNA sequencing over broad panel analyses

The further development of molecular cancer therapies is a focus at the National Center for Tumor Diseases (NCT/UCC) Dresden, a joint institution of the German Cancer Research Center with the Medical Faculty of the TU Dresden, the University Hospital Dresden and the Helmholtz-Zentrum Dresden-Rossendorf. Among other things, genome sequencing is of great interest here, in which the genetic material of a cell is analyzed as comprehensively as possible. Differences between tumor cells and healthy cells are used to identify and exploit new starting points for targeted therapy. In practice, different comprehensive techniques are used to search for these changes. Scientists from the Department of Translational Medical Oncology at the NCT/UCC have compared two different sequencing methods to examine the influence of the choice of methodon molecular therapy recommendations and implementation in patients with advanced tumor diseases.

Cancer is caused by changes in the genetic material of cells that distinguish them from healthy cells and lead to uncontrolled growth. However, these changes can also be starting points for targeted treatment. It can therefore be important to identify them and take them into account when planning treatment. However, the sequencing methods used for this can differ in type and scope. In the study "Translational and clinical comparison of whole genome and transcriptome to panel sequencing in precision oncology", researchers investigated whether whole genome and RNA sequencing (WGS/TS) enables more targeted therapy recommendations and actual therapy implementation compared to panel sequencing, which is limited to 523 tumor-relevant genes at DNA level.

Tumor samples from 20 people with rare or advanced cancers were analyzed using both methods and the resulting therapy recommendations and underlying molecular biomarkers were compared. The results show that about half of the recommendations from both sequencing methods matched, while about a third of the recommendations from whole genome and RNA sequencing were based on biomarkers that cannot be detected by panel sequencing. In two cases, this led to additional treatment conversions that would not have been possible with panel sequencing alone.

The study represents an important comparison of molecular therapy recommendations of different sequencing methods," explains Dr. Irina Kerle, first author of the study. For clinical application, the results make it clear that comprehensive sequencing can reveal valuable additional therapy options in certain cases," emphasizes Professor Stefan Fröhling, Managing Director of the NCT in Heidelberg and co-initiator of the MASTER program.

The research results illustrate that broad panel sequencing is already revealing numerous new treatment options for patients with rare or advanced tumors whose treatment was previously limited. According to Kerle, the fact that in some cases whole genome and transcriptome sequencing leads to additional therapy recommendations and implementations underlines the need to expand this sequencing method in the future. "I am delighted that our department offers both sequencing programs at the Dresden site. This allows us to contribute to the expansion of molecular therapy options with translational and clinical research projects," she emphasizes.

"The study once again shows the importance of comprehensive molecular analyses for personalized tumor therapy, especially for rare and difficult-to-treat tumor diseases," explains Prof. Hanno Glimm, Managing Director and Head of the Department of Translational Medical Oncology at the NCT/UCC, and spokesperson for the Center for Personalized Medicine in Oncology (ZPMO). "With the participation of the University Hospital in the recently launched genome sequencing model project, we can continue along this promising path. The fact that health insurance companies will cover the costs of genome analysis means that more patients than before will have the opportunity to tailor their treatment to their individual molecular tumor profile."

The sequencing programs
DKFZ/NCT/DKTK MASTER program for rare advanced tumor diseases and MASTERsg program for advanced tumor diseases with foreseeable exhaustion of standard therapy: https://www.nct-dresden.de/de/fuer-patienten/behandlung/vom-gen-zur-therapie-das-nct-dktk-master-programm

Publication:
"Translational and clinical comparison of whole genome and transcriptome to panel sequencing in precision oncology ": https://doi.org/10.1038/s41698-024-00788-3

Contact:
Dr. Irina Kerle
Translational Medical Oncology
National Center for Tumor Diseases Dresden (NCT/UCC)
irina.kerle@nct-dresden.de
www.nct-dresden.de

Prof. Hanno Glimm
Head of the Department
Translational Medical Oncology
hanno.glimm@nct-dresden.de
Phone: +49 (0) 351 458 5531