cancer-research-structural-biochemistry-2019-posters

Page 51

Volume 3

August 5-6, 2019 | Singapore

CANCER RESEARCH AND PHARMACOLOGY

STRUCTURAL BIOCHEMISTRY, STEM CELLS AND MOLECULAR BIOLOGY

International Conference on

International Congress on

Cancer Research 2019 & Structural Biochemistry 2019

August 5-6, 2019

Journal of Cancer and Metastasis Research

Detection of mutations in hTERT gene promoter sequence without DNA amplification

by novel SERRS sensor for cancer diagnostics

Zvereva M

Lomonosov MSU, Russia

ecently developed liquid biopsy analysis based on circulating tumor DNA (ctDNA) released by tumor cells in body liquids

significantly enhanced non-invasive molecular diagnostics of cancer as ctDNA contains all mutations generated in the

tumor. For example, mutations in the promoter of telomerase catalytic subunit (TERT) gene are highly specific for multiple

cancers, including bladder cancer. Thus, selective determination of such mutations can improve early diagnostics of cancer and

monitoring of cancer progression and treatment. Main limitations for existing methods of ctDNA detection in body fluids are:

a) a low portion of tumor DNA in comparison to wild type circulating DNA that results in poor sensitivity, especially in case of

preliminary DNA amplification and b) high fragmentation of cell free DNA that complicates DNA purification. In this regard,

novel approaches without DNA isolation and amplification for specific detection of tumor DNA are of unmet medical need.

Spectroscopy Resonance Raman Scattering (SERRS) allows detection of target molecules in multicomponent complex mixtures

without isolation at fM concentrations due to the resonant enhancement of the signal. To apply this approach, we developed

SERS-active colloids based on silver nanoparticles deposited on planar sensor surfaces. Short oligonucleotide probes were

immobilized on silver nanoparticles using anchor sequences. As a result, we were able to detect DNA with TERT promoter

sequence from femtomolar to micromolar concentration with the linear response of SERRS signal.

The study was supported by Russian Foundation of Basic Research grant № 18-29-08040.

Biography

Zvereva M has her expertise in investigation of telomerase as molecular target for anticancer drug development and base of new

molecular tests for diagnostics of oncogenic process. Her research group was concentrated on understanding of telomerase functioning

and regulation using biochemical and bioengineering approaches for model organisms. They optimized the telomerase activity tests

and used it in different ways (Biochemie, 2013; Mol Cell Biol., 2014; and etc.), created two novel classes of telomerase inhibitors for

future anti-cancer therapy development (J Med Chem. 2014; Nucleic Acids Res., 2014) and one of them could be used possibly for

diagnostics (Biochemistry (Moscow), 2015, review). The screening of telomerase activation in clinical samples and assessing the

potential role of splicing events during activation of telomerase was done for cervical cancer and pre-cancerous lesion (Biochimie,

2010). As a scientist of IARC she participated in development of method for detection of mutations in hTERT gene promoter sequence

for bladder cancer diagnostics (EBiomedicine, 2019).