Læknablaðið : fylgirit - 03.01.2017, Blaðsíða 56

X V I I I V Í S I N D A R Á Ð S T E F N A H Í
F Y L G I R I T 9 1
56 LÆKNAblaðið/Fylgirit 91 2017/103
og þeir voru hlutfallslega meira í tölvuleikjum en síður á internetinu, sam-
anborið við stúlkur. Einkenni um þunglyndi, kvíða og líkamleg óþægindi
voru algengari hjá stúlkum en drengjum. Skjátími og áköf hreyfing
tengdust andlegri líðan, bæði sjálfstætt og víxlverkandi. Þeir sem voru í
efri helmingi hópsins með tilliti til skjátíma voru líklegri til að greina frá
einkennum um þunglyndi (OR=4,1 (CI:1,6-10,7)), kvíða (OR=3,2 (CI:1,4-
7,2)) og líkamleg óþægindi (OR=2,3 (CI:1,1-5,1)). Minni áköf hreyfing (≤3x/
viku) var marktækt tengd einkennum um þunglyndi (OR=3,8 (CI:1,6-9,5))
og kvíða (OR=4,5 (CI:2,0-10,0). Einkenni um andlega vanlíðan voru al-
gengust hjá þeim sem bæði voru mikið við skjá og stunduðu sjaldan ákafa
hreyfingu.
Ályktanir: Kynjamunur var á mynstri og magni skjátíma svo og tíðni ein-
kenna um andlega vanlíðan. Minni áköf hreyfing og meiri heildarskjátími
virðast vera í tengslum við verri andlega líðan meðal íslenskra unglinga,
sérstaklega þegar hvorttveggja fer saman.
E 165 The role of ALKBH3 in epigenetics, DNA repair, and breast
cancer
Stefán Hermanowicz, Þorkell Guðjónsson, Ólafur A. Stefánsson, Jórunn E. Eyfjörð,
Stefán Þ. Sigurðsson
University of Iceland
sthh16@hi.is
Introduction: DNA repair is crucial to maintaining the health and in-
tegrity of cells. Damage that is allowed to persist within the DNA may
aid in the formation of diseases such as cancer. It is therefore crucial
that proteins involved in DNA repair are functional. Incidences where
protein expression is impaired have been linked to disease formation.
Epigenetic modification, particularly promoter methylation, can cause
a downregulation of gene expression. Through database analysis we
identified 5 repair proteins which undergo promoter methylation, one
of which being ALKBH3. ALKBH3 is a protein responsible for the repair
of a form of DNA alkylation damage, specifically 3-methylcytosine.
According to The Cancer Genome Atlas, 20% of breast cancers are
promoter methylated for ALKBH3. We also found this to occur in a
subset of Icelandic tumor tissues. Importantly, epigenetic silencing
of ALKBH3 is occurring within tumors and not the normal tissue of
the same patients. Additionally our data shows ALKBH3 is having an
impact on the functionality of a key Double-Stranded Break (DSB) repair
protein. Our research aims to elucidate this potential role of ALKBH3 in
DSB repair and exploit the downregulation of this protein by looking for
potential synthetic lethality.
Methods and Data: Database Mining. Pyrosequencing. Molecular
Cloning. Western Blot. siRNA. qPCR.
Results: Icelandic patients with ALKBH3 methylation (5%) showed decre-
ased survival. ALKBH3 is functionally impacting DSB repair.
Conclusions: ALKBH3 may be a novel biomarker for certain chemother-
apeutic treatments due to its methylation status in tumor tissue and its
regulation of a key DSB repair protein
E 166 Telomere length measurements in BRCA2 mutation carriers
using a multiplex monochrome qPCR method
Birna Þorvaldsdóttir1, Margrét Aradóttir2, Sigríður K. Böðvarsdóttir2, Jórunn E.
Eyfjörð2
1Cancer Research Laboratory, Faculty of Medicine, University of Iceland, 2Faculty of Medicine,
University of Iceland
bth60@hi.is
Introduction: Germline mutations in the BRCA2 gene increase the risk
of breast cancer and other malignancies. BRCA2 has been shown to play
a role in telomere protection and maintenance. Dysfunctional telomere
maintenance can cause excessive telomere shortening which can lead
to chromosomal instability. Telomere length (TL) has been studied as a
modifying factor for various diseases, including breast cancer. Previous
research on TL in BRCA mutation carriers has produced contradicting
results. The aim of our study was to determine whether TL measurements
could be used as a stratification method for breast cancer risk in BRCA2
mutation carriers.
Methods: TL was measured in over 1200 DNA samples from female
BRCA2 mutation carriers, their non-carrier relatives, sporadic breast
cancer patients and healthy controls. Measurements were performed
using a high-throughput monochrome multiplex qPCR method.
Results: We find no difference in mean TL between mutation carriers,
sporadic breast cancer patients or controls. Using samples acquired before
breast cancer diagnosis we see shorter telomeres being significantly
associated with breast cancer incidence in BRCA2 mutation carriers. We
see no association with breast cancer specific survival, subtypes or other
clinical parameters.
Conclusion: Based on our preliminary results, TL measurements might
be of use as additional information in breast cancer risk stratification for
BRCA2 mutation carriers and merits further research.
E 167 Defining metabolic pathways in isogenic breast epithelial and
mesenchymal cell lines with stable isotope tracing
Skarphéðinn Halldórsson1, Freyr Jóhannsson2, Siver A. Moestue3, Óttar Rolfsson2
1Center for Systems Biology, University of Iceland, 2Department of Medicine, UI, 3Department
of Medical Imaging, NTNU
skarph@hi.is
Introduction: Cancer metabolism has gained increasing attention in the
recent decade. Multiple metabolic alterations in neoplasia have been
described to date, such as increased demand for glucose and glutamine as
metabolic fuels and decreased dependence on oxygen. We have recently
constructed genome scale metabolic models of distinct epithelial and
mesenchymal phenotypes on the same genetic background as a method
to study metabolic alterations in epithelial to mesenchymal transition
(EMT). Here, we use stable isotope tracing to validate model predictions
and provide ratiometric information on intracellular metabolic pathways.
Methods: D492 epithelial cells and D492M mesenchymal cells were
fed 1-13C1 glutamine or 1,2-13C2 glucose for 6 hours, internal metabolites
collected and measured with UPLC-MS and NMR. Labeled and unlabeled
fractions were used to calculate flux ratios at metabolic junctions.
Results: Both phenotypes metabolize glutamine primarily in the TCA
cycle although it is also used to maintain glutathion and proline pools.
D492 cells exclusively metabolize glutamine via oxidative phosphor-
ylation in the TCA cycle while D492M cells divert a substantial fraction
of glutamine to citrate production via reductive carboxylation. These data