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and Radiology of Serbia (IORS) in 2008, with the aim to provide a personalized
approach to cancer treatment of Serbian patients. First mutation detection analy-
sis was performed in the KRAS gene in patients with metastatic colorectal cancer
(mCRC). Between April 2008 and December 2016, 2346 patients diagnosed with
mCRC have been tested for KRAS mutations and starting from January 2017, 146
patients have been tested for all RAS.
EGFR mutation testing of advanced non-small cell lung cancer patients for tar-
geted therapy with small tyrosine kinase inhibitors (TKIs) became a part of rou-
tine clinical practice in Serbia since 2011. Until May 2017, 3750 patients have been
tested for the presence of EGFR mutations. Knowledge of acquired resistance
mechanisms to EGFR TKIs was one of the triggers behind the development of
personalized therapies, with the introduction of the third-generation EGFRTKIs,
which are active against sensitive, as well as resistant T790M EGFR mutations. In
summer 2016, T790M mutation detection in circulating tumour DNA (ctDNA) iso-
lated from blood samples in EGFR-mutant NSCLC patients with progression under
first- or second-generation EGFR TKIs was introduced in our clinical practice.
Two recently introduced analyses are BRAF mutation detection in patients with
metastatic melanoma in order to select patients for targeted therapy and somatic
BRCA1/2 mutation testing in ovarian carcinoma to identify patient’s eligibility for
treatment with PARP inhibitors.
Further advances in DNA technologies and bioinformatics will allow further inte-
gration of somatic mutation testing in the management for all malignancies.

Clinical significance of epigenetic alterations in cancer LECTURES

Zvonko Magić

Institute for medical research, Military Medical Academy, School of Medicine, University of
Defense, Belgrade, Serbia

Epigenetic modifications are heritable changes in gene expression that are not BOOK ABSTRACT
coded in the DNA sequence. Recently investigations showed that the number of
cancer-related genes that are inactivated by epigenetic modifications equals or
even exceeds the number of genes inactivated by mutations. Major mechanisms 2
of epigenetic control in mammals are DNA methylation, histone modifications and
RNA interference (RNA silencing). The key epigenetic modification in mammals is