Next-Generation Sequencing

To successfully treat a tumor disease and to provide personalized targeted therapy for the individual patient it is crucial to carry out a series of analysis on a molecular level. The so called next-generation sequencing (NGS) is one of these methods.

In 1977 the chain termination method has been first described by Sanger, which was based on the electrophoretic separation of fragments and was suffering from a lot of disadvantages (e.g. time consuming, cost expensive…). During the past years there has been a rapid development regarding technical as well as financial aspects of sequencing technologies. Due to its high demand and growing importance as a diagnostic and research tool, it is now possible to sequence a human genome in less than two weeks for about 5000 USD.

Since the second generation sequencing methods (NGS methods) display very high sensitivity compared to the conventional sequencing methods. This allows the usage of NGS not only for research but also for clinical diagnostics. With this method you can detect pathological changes in the DNA such as mutations in the tumor or blood of the patient. Hence the therapy of the patient can be adjusted individually depending on the genetic characteristics and mutational status of the tumor, allowing a targeted tumor therapy.

In our laboratory, we developed a 327 gene panel especially for tumors of the head and neck region. The technology we use is the HaloPlex Target Enrichment System from Agilent, which shows high sensitivity and therefore even allows the detection of mutations with low allele frequency.

The aim of this project is to compare primary and relapse tumor tissue from one and the same patient to search for mutations, which are either occurring during the course of the disease or are due to specific forms of treatment. Due to the fact that there are no hotspot mutations in tumors of the head and neck region like for example in the KRAS gene of patients suffering from colorectal cancer, it is even more important to better understand the molecular characteristics of these tumors and to improve the tumor therapy by finding new druggable targets.

summary:

• Studying the genetic differences of primary and recurrent tumor tissue and analyze the mutational load of the samples
• Obtaining a better understanding of the molecular mechanisms of the tumor, to improve tumor therapy
• Identifying new therapeutic drug targets