Thesis topic proposal
Genetic instability as the driver of carcinogenesis


Institute: University of Szeged
theoretical medicine
Graduate School of Multidisciplinar Medical Scienses

Thesis supervisor: Lajos Mátés
Web address (URL): http://www.brc.hu/gen_genome_instability_and_carcinogenesis_unit.php
Location of studies (in Hungarian): Biological Research Centre of the Hungarian Academy of Sciences, Institute of Genetics, H-6726 Szeged, Temesvári krt. 62.
Abbreviation of location of studies: SZBK

Description of the research topic:

Cancer is the leading cause of death in the developed world. According to estimates from the International Agency for Research on Cancer, there were 8.2 million cancer deaths in 2012 worldwide and by 2030 the global burden is expected to grow to 13 million deaths simply due to the growth and aging of the population.
Cancer development can be considered as an evolutionary process within our body, driven by genetic instability generating genetic variations and natural selection analogous to Darwinian evolution. Significant emphasis has recently been placed on the characterization of the human cancer genome. However, the genetic complexity of cancer has complicated the identification of the so called "driver" mutations facilitating disease progression, among the more abundant “passenger” mutations found in tumours. To date ~140 "driver" genes with mutations conferring a selective growth advantage to the tumour cells have been reliably identified. Importantly, methods based on mutation frequency alone can only prioritize but cannot unambiguously identify "driver" genes. Accordingly, besides the continuation of tumour sequencing efforts, the scientific world is currently shifting the focus on functional studies to identify "driver" mutations and explore that how they influence the development and progression of cancer.
The harmful "driver" mutations typically occur somatically during cancer development. Consequently, classical transgenic animals, produced by the modification of the germline, are frequently inadequate for the creation/testing of such mutations. Lately we have developed an alternative method for somatic transgenesis in mice, based on an ex vivo gene therapy protocol, avoiding the modification of the germline and allowing the rapid in vivo analysis of artificially created "driver" mutations.
The complexity of alterations seen in cancer genomes develops as a consequence of the well known genetic instability of cancer cells, which generates the genetic diversity facilitating tumour evolution. We will investigate a range of cellular processes to explore errors fuelling malignant transformation by undermining genome integrity. To achieve our goal we will use our state-of-the-art animal models and gene transfer technologies.

Required language skills (in Hungarian): English
Further requirements (in Hungarian): 
TDK munka

Number of students who can be accepted: 1

Deadline for application: 2017-07-31

2017. I. 31.
ODT ülés
Az ODT következő ülésére 2017. március 10-én 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).

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