Genetic and epigenetic alterations of human chromosome 3, investigated by NotI-microarrays in seven types of epithelial cancers
Aim. To identify common and specific genetic/epigenetic changes of human chromosome 3, using the data of NotI-microarrays in seven types of epithelial cancers. Methods. We used descriptive statistics for the comparative analysis of NotI-microarray data from seven types of epithelial cancers. Results...
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irk-123456789-1542772019-07-07T12:23:21Z Genetic and epigenetic alterations of human chromosome 3, investigated by NotI-microarrays in seven types of epithelial cancers Gerashchenko, G.V. Gordiyuk, V.V. Kashuba, V.I. Genomics, Transcriptomics and Proteomics Aim. To identify common and specific genetic/epigenetic changes of human chromosome 3, using the data of NotI-microarrays in seven types of epithelial cancers. Methods. We used descriptive statistics for the comparative analysis of NotI-microarray data from seven types of epithelial cancers. Results. The analysis of the NotI-microarrays showed significant changes (deletion or methylation) in 74 genes/loci in seven different epithelial cancers, namely colorectal, ovarian, renal, lung, breast, cervical and prostate. Five genes from the 3p14-3p24 region (FOXP1, LRRC3B, NKiRAS1, RBSP3, ZIC4) were altered in all cancer types. For fifteen genes, deletion/methylation was found in a majority of tumors. For example, ITGA9, GORASP1, IQSEC1, CGGBP1, NBEAL2 and VHL are localized in the 3p12-3p26 region; PPP2R3A, FGF12, ALDH1L1, GATA2 and PLCL2 are localized the 3q13-3q28 region. Twenty-two genes out of 74 studied showed alterations specific for a single type of tumor. The largest number, 13 genes/loci was found in the prostate cancer. This suggests specific mechanisms of prostate cancer development. Conclusions. NotI-microarrays for human chromosome 3 allowed to identify several common genetic/epigenetic alterations and also tumor-specific changes in seven types of epithelial cancer. Мета. Знайти загальні та специфічні генетичні / епігенетичні зміни хромосоми людини 3, за допомогою NotI-мікропанелей у епітеліальних новоутвореннях семи різних локалізацій. Методи. Було використано методи дескриптивної статистики для порівняльного аналізу даних NotI-мікропанелей у семи локалізаціях злоякісних пухлин. Результати. Порівняльний аналіз даних NotI-мікропанелей показав значні зміни / метилування 74 генів / локусів у семи локалізаціях раку (товстої кишки, яєчників, нирок, легенів, молочних залоз, шийки матки, передміхурової залози). П’ять генів мають зміни у всіх 7 типах раку (FOXP1, LRRC3B, NKiRAS1, RBSP3, ZIC4). Вони були в основному з 3p14-3p24 регіону. П’ятнадцять генів мають делецію / метилювання в 6 та 5 локалізаціях раку. Серед них гени/локуси розташовані приблизно у 3p12-3p26 регіоні (ITGA9, GORASP1, IQSEC1, CGGBP1, NBEAL2, VHL), 3q13-3q28 регіоні (PPP2R3A, FGF12, ALDH1L1, GATA2, PLCL2). Двадцять два гени з 74 мають зміни тільки в одній локалізації раку. Переважна кількість їх (13 генів / локусів) зустрічається для раку передміхурової залози. Це може свідчити про специфічні механізми канцерогенезу передміхурової залози, які відрізняються від інших локалізацій. Висновки. Аналіз та узагальнення даних NotI- мікропанелей хромосоми 3 людини показали, як кілька загальних змін раку серед семи локалізацій раку, так і деякі специфічні пухлинні зміни, які могли б характеризувати особливі канцерогенезу певного виду пухлин. Цель. Установить общие и специфичные для опухолей генетические / эпигенетические изменения хромосомы 3 человека с помощью NotI-микропанелей в эпителиальных новобразованиях при семи различных локализациях. Методы. Были использованы методы дескриптивной статистики для сравнительного анализа данных NotI-микропанелей в семи локализациях злокачественых опухолей. Результаты. Анализ NotI-микропанелей показал значительные изменения делеции / метилирования 74 генов / локусов в семи локализациях рака (толстой кишки, яичника, почек, легких, груди, шейки матки, предстательной железы). Пять генов имеют изменения во всех 7 типах рака (FOXP1, LRRC3B, NKiRAS1, RBSP3, ZIC4). Они были в основном из региона 3p14-3p24. Пятнадцать генов имеют делецию / метилирование в 6 и 5 локализациях рака. Среди них есть в регионе 3p12-3p26 (ITGA9, GORASP1, IQSEC1, CGGBP1, NBEAL2, VHL), в пределах 3q13-3q28 региона (PPP2R3A, FGF12, ALDH1L1, GATA2, PLCL2). Двадцать два гена из 74 имеют изменения только в одной локализации рака. Преобладающее число из них (13 генов / локусов) обнаружено для рака предстательной железы. Это может указывать на конкретные механизмы канцерогенеза предстательной железы, которые отличаются от других локализаций. Выводы. Анализ и обобщение данных NotI-микропанели хромосомы человека 3 показало, что несколько распространенных изменений рака среди семи локализаций рака, как несколько изменений в опухоли, которые могут характеризовать его особые канцерогенные признаки.Ключевые слова: NotI-микропанели, рак толстой кишки, рак яичников, рак почки, рак легких, рак шейки матки, рак молочной железы, рак предстательной железы, гены-супрессоры роста опухолей, метилирование, делеция, хромосома 3 человека. 2018 Article Genetic and epigenetic alterations of human chromosome 3, investigated by NotI-microarrays in seven types of epithelial cancers / G.V. Gerashchenko, V.V. Gordiyuk, V.I. Kashuba // Вiopolymers and Cell. — 2018. — Т. 34, № 4. — С. 303-312. — Бібліогр.: 37 назв. — англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.000983 http://dspace.nbuv.gov.ua/handle/123456789/154277 577.218+616.65 en Інститут молекулярної біології і генетики НАН України Вiopolymers and Cell |
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Genomics, Transcriptomics and Proteomics Genomics, Transcriptomics and Proteomics |
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Genomics, Transcriptomics and Proteomics Genomics, Transcriptomics and Proteomics Gerashchenko, G.V. Gordiyuk, V.V. Kashuba, V.I. Genetic and epigenetic alterations of human chromosome 3, investigated by NotI-microarrays in seven types of epithelial cancers Інститут молекулярної біології і генетики НАН України |
| description |
Aim. To identify common and specific genetic/epigenetic changes of human chromosome 3, using the data of NotI-microarrays in seven types of epithelial cancers. Methods. We used descriptive statistics for the comparative analysis of NotI-microarray data from seven types of epithelial cancers. Results. The analysis of the NotI-microarrays showed significant changes (deletion or methylation) in 74 genes/loci in seven different epithelial cancers, namely colorectal, ovarian, renal, lung, breast, cervical and prostate. Five genes from the 3p14-3p24 region (FOXP1, LRRC3B, NKiRAS1, RBSP3, ZIC4) were altered in all cancer types. For fifteen genes, deletion/methylation was found in a majority of tumors. For example, ITGA9, GORASP1, IQSEC1, CGGBP1, NBEAL2 and VHL are localized in the 3p12-3p26 region; PPP2R3A, FGF12, ALDH1L1, GATA2 and PLCL2 are localized the 3q13-3q28 region. Twenty-two genes out of 74 studied showed alterations specific for a single type of tumor. The largest number, 13 genes/loci was found in the prostate cancer. This suggests specific mechanisms of prostate cancer development. Conclusions. NotI-microarrays for human chromosome 3 allowed to identify several common genetic/epigenetic alterations and also tumor-specific changes in seven types of epithelial cancer. |
| format |
Article |
| author |
Gerashchenko, G.V. Gordiyuk, V.V. Kashuba, V.I. |
| author_facet |
Gerashchenko, G.V. Gordiyuk, V.V. Kashuba, V.I. |
| author_sort |
Gerashchenko, G.V. |
| title |
Genetic and epigenetic alterations of human chromosome 3, investigated by NotI-microarrays in seven types of epithelial cancers |
| title_short |
Genetic and epigenetic alterations of human chromosome 3, investigated by NotI-microarrays in seven types of epithelial cancers |
| title_full |
Genetic and epigenetic alterations of human chromosome 3, investigated by NotI-microarrays in seven types of epithelial cancers |
| title_fullStr |
Genetic and epigenetic alterations of human chromosome 3, investigated by NotI-microarrays in seven types of epithelial cancers |
| title_full_unstemmed |
Genetic and epigenetic alterations of human chromosome 3, investigated by NotI-microarrays in seven types of epithelial cancers |
| title_sort |
genetic and epigenetic alterations of human chromosome 3, investigated by noti-microarrays in seven types of epithelial cancers |
| publishDate |
2018 |
| topic_facet |
Genomics, Transcriptomics and Proteomics |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/154277 |
| citation_txt |
Genetic and epigenetic alterations of human chromosome 3, investigated by NotI-microarrays in seven types of epithelial cancers / G.V. Gerashchenko, V.V. Gordiyuk, V.I. Kashuba // Вiopolymers and Cell. — 2018. — Т. 34, № 4. — С. 303-312. — Бібліогр.: 37 назв. — англ. |
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Інститут молекулярної біології і генетики НАН України |
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| fulltext |
303
G. V. Gerashchenko, V. V. Gordiyuk, V. I. Kashuba
© 2018 G. V. Gerashchenko et al.; Published by the Institute of Molecular Biology and Genetics, NAS of Ukraine on behalf
of Biopolymers and Cell. This is an Open Access article distributed under the terms of the Creative Commons Attribution
License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any
medium, provided the original work is properly cited
UDC 577.218+616.65
Genetic and epigenetic alterations of human chromosome 3,
investigated by NotI-microarrays in seven types of epithelial cancers
G. V. Gerashchenko1, V. V. Gordiyuk1, V. I. Kashuba1,2
1 Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143
2 Karolinska Institute,
Stockholm SE-17177, Sweden
g.v.gerashchenko@imbg.org.ua
Aim. To identify common and specific genetic/epigenetic changes of human chromosome 3,
using the data of NotI-microarrays in seven types of epithelial cancers. Methods. We used
descriptive statistics for the comparative analysis of NotI-microarray data from seven types of
epithelial cancers. Results. The analysis of the NotI-microarrays showed significant changes
(deletion or methylation) in 74 genes/loci in seven different epithelial cancers, namely colo-
rectal, ovarian, renal, lung, breast, cervical and prostate. Five genes from the 3p14-3p24 region
(FOXP1, LRRC3B, NKiRAS1, RBSP3, ZIC4) were altered in all cancer types. For fifteen genes
deletion/methy lation was found in a majority of tumors. For example, ITGA9, GORASP1,
IQSEC1, CGGBP1, NBEAL2 and VHL are localized in the 3p12-3p26 region; PPP2R3A,
FGF12, ALDH1L1, GATA2 and PLCL2 are localized on the 3q13-3q28 region. Twenty-two
genes out of 74 studied showed alterations specific for a single type of tumor. The largest
number, 13 genes/loci was found in the prostate cancer. This suggests specific mechanisms of
prostate cancer development. Conclusions. NotI-microarrays for human chromosome 3 al-
lowed to identify several common genetic/epigenetic alterations and also tumor-specific
changes in seven types of epithelial cancer.
K e y w o r d s: NotI-microarray, colorectal cancer, ovarian cancer, renal cancer, lung cancer,
cervical cancer, breast cancer, prostate cancer, TSG, methy lation, deletion, human chromo-
some 3.
Introduction
E. Zabarovsky and V. Kashuba groups inves-
tigated genetic/epigenetic alterations in human
cancers by a large-scale method, named the
NotI-microarray, for more than fifteen years.
This method represents a comparative genome
hybridization technology (Karolinska Institute
International Patent WO02/086163 and PCT/
SE02/00788 [1]), based on hybridization of
the NotI-linking libraries, produced from tu-
mor and normal genomic DNA [2]. It makes
Genomics, Transcriptomics
and Proteomics
ISSN 1993-6842 (on-line); ISSN 0233-7657 (print)
Biopolymers and Cell. 2018. Vol. 34. N 4. P 303–312
doi: http://dx.doi.org/10.7124/bc.000983
mailto:g.v.gerashchenko@imbg.org.ua
304
G. V. Gerashchenko, V. V. Gordiyuk, V. I. Kashuba
possible, to determine both, the genetic (dele-
tions, amplifications) and epigenetic (methy-
lation, demethy lation) changes in the genomic
DNA of the NotI-linked genes / loci, due to
the sensitivity of the NotI restriction enzyme
to a methy lation status of CpG islands. Using
this technology, 181 NotI-linking clones from
different regions of human chromosome 3
were analyzed in more, than 250 malignant
tumor samples, derived from different organs
and tissues. [2, 3]. It is known that genetic and
epigenetic disturbances of chromosome 3 have
very important influence on carcinogenesis of
different human cancers [4–6]. On chromo-
some 3 several well-known and putative tumor
suppressor genes (TSG) as well as many can-
cer-associated genes are situated [3–7]. The
3p25-p26 region is harboring the well-known
TSG, such as VHL; 3p12-p14.2 region contains
the FHIT gene; 3p24 possesses the RARB gene
and 3p21-p22 region includes the RASSF1A
gene [8, 9]. However, a function and a role of
many other genes of chromosome 3, which
show alterations in different human cancer
types, were largely unknown, before the NotI-
microarray study.
The aim of the present work is to identify
common and specific genetic/epigenetic
changes of human chromosome 3, using the
data of NotI-microarrays in seven types of
epithelial cancer.
Materials and Methods
We have performed comparative analysis of
the NotI-microarray data for 7 types of epithe-
lial cancers [2, 10–18] using methods of de-
scriptive statistics. Fisher’s exact test and Chi-
square criteria were used for analysis of methy-
lation and/or deletion frequencies in groups of
tumors with different patho-morphological
characteristics [2, 10–18]. The cases with p-
value below 0.05 were considered statistically
significant. The Benjamini-Hochberg proce-
dure with false discovery rate (FDR) 0.20 was
used to correct p-value under multiple com-
parisons detection [19].
Results and Discussion
We have reviewed and summarized the data
from different cohorts and with different data
calculations for colorectal, ovarian, renal, lung,
breast, cervical and prostate cancers [2, 10–
18]. All the data represent epithelial tumors,
investigated by NotI-microarrays. A fragment
of NotI-microarray data is shown in Figure 1.
Notably, the greatest number of alterations
is hetero- and homozygous deletions or methy-
lation, in all reported data sets. Amplifications
and demethy lation were quite a rare event in
epithelial tumors in comparison with leuke-
mia [20]. Hence, deletions and methy lation
were in the focus of the present paper.
Altogether, we found that 74 genes / loci of
chromosome 3 exhibited significant changes in
seven types of epithelial tumors. These results
are presented in Table 1. It was found 40 genes/
loci with changes from 3p arm and 34 genes/
loci from 3q arm of chromosome 3. Five genes,
namely FOXP1, LRRC3B, NKIRAS1, RBSP3
and ZIC4 altered in all se ven studied tumor
types. They are located in the 3p14-3p24 region.
Five genes/loci, namely ITGA9, GORASP1,
IQSEC1, CGGBP1 and PPP2R3A, showed
genetic /epigenetic changes in six various types
of tumor. Ten genes/loci — WNT7A, NBEAL2,
VHL, LOC285205, FGF12, ALDH1L1, GATA2,
PLCL2, ABHD5/TOPAZ1, EPHB1 — had ge-
netic /epigenetic alterations in five cancer types.
305
Noti-microarrays alterations in seven cancer types
NKiRAS1 3p24.2
RARbeta1 3p24
FLJ44898 3q21.1
CGGBP 3p12
ITGA9 3p21.3
MINT24 3p25-3p26
LRRC3B 3p24
LOC732138 3P21.32
ROPN1 3q21.1
GATA-2 3q21.3
PRICKLE2 3p14
NotI0105 ALDH1L1 3q21.2
NotI0111 GATA2 3q21.3
NotI0043 GORASP1 3p22-p21.33
NotI0085 FOXP1 3p14.2
NotI0141 RAP2B 3q25.2
NotI0008 VHL 3p26-p25
NotI0055 NBEAL2 3p21.31
NotI0097 LOC285205 3q13.12
NotI0106 CHST13 3q21.2
NotI0074 BHLHB2 3p26
NotI0139 ZIC4 3q24
NotI0028 UBE2E2 3p24.2
NotI0062 GNAI2 3p21
NotI0107 LOC650370 3q21.2
NotI0121 TRH 3q21.3
NotI0125 KY 3q22.1
NotI0127 PPP2R3A 3q21.1
NotI0166 FGF12 3q28
NotI0019 WNT7A 3p25
NotI0012 RPL32 3p25.3
NotI0163 BCL6 3q27
NotI0142 GPR149 3q25.2
NotI0149 SOX2 3q26.3
NotI0180 THRB 3p24.3
NotI0026 PLCL2 3p24.3
NotI0041 RBSP3 3p21.33
NotI0048 SNRK 3p22.1a
NotI0054 TESSP2 3p21.31
NotI0091 MINA 3q11.2
NotI0169 C3ORF21 3q28
NotI0177 DHX30 3p21.31
NotI0003 LMCD1 3p26-p24
NotI0084 MITF 3p14.1
NotI0145 B3GALT3 3q25
NotI0013 IQSEC1 3p25.2
Spot No Gene/loci Location
NotI0029
NotI0031
NotI0126
NotI0090
NotI0040
NotI0001
NotI0033
NotI0050
NotI0103
NotI0110
NotI0079
1 stage 2 stage 3-4 stage
Fig. 1. A fragment of NotI-microarray data in breast tumors. Green and dark green with hatching squares: methylation/
deletion (< 0.85), red: amplification/demethylation (> 1.5), yellow: unchanged (> 0.85, < 1.5), and white: no info.
(grey and dark grey with hatching squares: methylation/deletion (< 0.85), black: amplification/demethylation (> 1.5),
light grey: unchanged (> 0.85, < 1.5), and white: no info)
Genes GORASP1, IQSEC1, CGGBP1, NBEAL2
and VHL are localized in the 3p12-3p26 region;
genes PPP2R3A, FGF12, ALDH1L1, GATA2
and PLCL2 are situated in the 3q13-3q28 re-
gion. A large number of genes with the same
changes in different epithelial tumors suggests
the common mechanisms of cancer develop-
ment and the function of these genes as putative
tumor suppressor genes.
Twenty-two genes out of 74 have alterations
only in the single type of tumor. The major
part of them (13 genes / loci) is found in pros-
306
G. V. Gerashchenko, V. V. Gordiyuk, V. I. Kashuba
Table 1. Genes and loci of chromosome 3 with changes (deletion/methylation) in seven types of epithelial
cancers
307
Noti-microarrays alterations in seven cancer types
Continued Table 1
308
G. V. Gerashchenko, V. V. Gordiyuk, V. I. Kashuba
tate cancer. This may indicate specific mecha-
nisms of carcinogenesis of the prostate that are
different from other localizations.
Noteworthy, earlier many investigations
have been focused on studying the genes of
the 3p arm of the chromosome 3 [2, 5, 6],
whereas little attention has been paid to the
genes of the 3q arm. The results of NotI-
microarrays show the involvement of 3q arm
genes / loci in the carcinogenesis of epithelial
tumors of all seven localizations. For example,
the ZIC4 gene encodes the Zic family member
4 that is important in the development.
It participates in the regulation of transcrip-
tion by RNA-polymerase II, but it has very
low expression levels. It has deletion/me thy-
lation changes in all seven tumor localization.
Our data are confirmed by other researchers
on another type of epithelial cancer (bladder
cancer) [21]. Importantly, these epigenetic
changes could be detected in biological fluids,
such as urine, while it is impossible to detect
the ZIC4 expression levels.
Another gene from 3q arm with deletion/
methy lation changes in 6 tumor localizations
is PPP2R3A. This gene encodes one of the
regulatory subunits of the protein phospha-
tase 2, which is implicated in the negative
control of cell growth and division [22].
However, the genetic/epigenetic changes of
this gene in epithelial cancers were not known
until our studies.
Four genes from 3q arm, which have dele-
tion/methy lation in 5 localizations of epithe-
lial tumors are FGF12, ALDH1L1, GATA2,
EPHB1. FGF12 is a member of the FGF fam-
ily which is involved in a variety of biological
processes, including cell growth, morpho ge-
nesis, tissue repair, tumor growth, and inva-
sion [23]. The methy lation of FGF12 in
colorectal cancers was shown [24]. Our study
has confirmed this type of the FGF12 epigen-
etic changes in prostate cancer [18]. It is re-
vealed as a putative biomarker in esophageal
cancer [25]. The ALDH1L1 gene encodes the
aldehyde dehydrogenase 1 family member L1.
Loss of function (epigenetic silencing) or ex-
pression of ALDH1L1 is associated with in-
creased cell motility, decreased apoptosis and
cancer progression [26]. On the other hand,
ALDH1L1 is the indicative gene of cancer cell
stemness and it is a biomarker in colon cancer,
which is associated with worth prognosis [27].
Continued Table 1
Notes: OC — ovarian cancer; ColC — colorectal cancer; BC — breast cancer; CervC — cervical cancer; LC — lung
cancer; ccRCC — clear cell renal cell carcinoma; PC — prostate cancer; * — genes / loci with significant differences
with FDR = 0.2.
309
Noti-microarrays alterations in seven cancer types
GATA2 encodes a member of the GATA fam-
ily of zinc-finger transcription factors. It con-
ducts transcriptional signals in particular from
the androgen receptor [28]. GATA2 has a mul-
tifaceted function in prostate cancer aggres-
siveness and is a highly attractive target for
treatments of lethal prostate cancer [29]. The
GATA2 expression is associated with poor
prognosis in acute myeloid leukemia [30]. The
EPHB1 gene encodes a transmembrane protein
which is a receptor for ephrin-B1. Loss of the
ephrin receptor (EphB1) expression may be
associated with aggressive cancer phenotypes
in acute myelogenous leukemia [31]. The tu-
mor suppressor function of EPHB1 in breast,
colon and lung cancers was shown [32].
Noteworthy, the alterations of many genes
(ITGA9, LRRC3B, FGF12, GORASP1,
NKIRAS1, CTDSPL (RBSP3), GATA2,
SEMA3B, IQSEC1, PPM1M1, PRICLE2,
BHLHE40 et al.), which were found by NotI-
microarrays, have been confirmed by other
methods, such as LOH, MSP, bisulfite sequenc-
ing, deletion analysis and expression studies
[10–18]. The TSG function for several genes
was confirmed in model systems (cell lines,
experimental animals), using transient and con-
stitutive expression of these genes [33–35].
Moreover, we have investigated genetic/
epigenetic changes and expression of some
genes, which have no NotI-site, from well-
known TSG RASSF1A 3p21.31 region. We have
shown deletion/methy lation changes by NotI-
microarray in some tumor localization of genes
from this region (3p21.31) named NBEAL2,
GNAI2, TOPAZ1. Our study has confirmed ge-
netic/epigenetic changes and loss of expression
for GPX1 and SEMA3B in renal and lung can-
cers [35–37]. Data of other investigators have
revealed the down regulation of HYAL1, HYAL2,
RASSF1A (3p21.31 region) in non-small cell
lung cancer [34]. These data indicate the mul-
tiple inactivation of TSG and potential TSG
clusters in human chromosome 3.
Conclusions
The analysis of the data, obtained with NotI-
microarrays for human chromosome 3, identi-
fied several common genetic/epigenetic al-
terations in seven types of epithelial cancer
and tumor-specific changes as well. These data
make a basis for the creation of special sets of
markers for early diagnostics, prediction of a
course of disease, and evaluation of efficacy
and a choice of therapy.
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Генетичні та епігенетичні порушення
хромосоми 3 людини, визначені за допомогою
NotI-мікропанелей в сімох локалізаціях
епітеліальних злоякісних пухлин
Г. В. Геращенко, В. В. Гордіюк, В. І. Кашуба
Мета: Знайти загальні та специфічні генетичні / епі-
генетичні зміни хромосоми людини 3, за допомогою
NotI-мікропанелей у епітеліальних новоутвореннях
семи різних локалізацій. Методи: Було використано
методи дескриптивної статистики для порівняльного
аналізу даних NotI-мікропанелей у семи локалізаціях
злоякісних пухлин. Результати. Порівняльний аналіз
даних NotI-мікропанелей показав значні зміни / мети-
лування 74 генів / локусів у семи локалізаціях раку
(товстої кишки, яєчників, нирок, легенів, молочних
залоз, шийки матки, передміхурової залози). П’ять
генів мають зміни у всіх 7 типах раку (FOXP1, LRRC3B,
NKiRAS1, RBSP3, ZIC4). Вони були в основному з
3p14-3p24 регіону. П’ятнадцять генів мають делецію
/ метилювання в 6 та 5 локалізаціях раку. Серед них
гени/локуси розташовані приблизно у 3p12-3p26 регі-
оні (ITGA9, GORASP1, IQSEC1, CGGBP1, NBEAL2,
VHL), 3q13-3q28 регіоні (PPP2R3A, FGF12, ALDH1L1,
GATA2, PLCL2). Двадцять два гени з 74 мають зміни
тільки в одній локалізації раку. Переважна кількість їх
(13 генів / локусів) зустрічається для раку передміху-
рової залози. Це може свідчити про специфічні меха-
нізми канцерогенезу передміхурової залози, які від-
різняються від інших локалізацій.Висновки: Аналіз
даних NotI-мікропанелей 3-ї хромосоми людини вия-
вив ряд як загальних генетичних/епігенетичних по-
рушень, так і пухлино-специфічні зміни.
К л юч ов і с л ов а: NotI-мікропанелі, рак товстої
кишки, рак яєчників, рак нирки, рак легенів, рак ший-
ки матки, рак молочної залози, рак передміхурової
залози, гени-супресори росту пухлин, метилювання,
делеція, хромосома 3 людини.
Генетические и эпигенетические изменения
хромосомы 3 человека, определённые с помощью
NotI-микропанелей в семи локализациях
эпителиальных злокачественных опухолей
А. В. Геращенко, В. В. Гордиюк, В. И. Кашуба
Цель: Установить общие и специфичные для опухолей
генетические / эпигенетические изменения хромосомы
3 человека с помощью NotI-микропанелей в эпители-
альных новобразованиях при семи различных локали-
зациях. Методы: Были использованы методы дес-
криптивной статистики для сравнительного анализа
данных NotI-микропанелей в семи локализациях зло-
качественых опухолей. Результаты. Анализ NotI-
микропанелей показал значительные изменения деле-
ции / метилирования 74 генов / локусов в семи лока-
лизациях рака (толстой кишки, яичника, почек, легких,
груди, шейки матки, предстательной железы). Пять
генов имеют изменения во всех 7 типах рака (FOXP1,
LRRC3B, NKiRAS1, RBSP3, ZIC4). Они были в основ-
ном из региона 3p14-3p24. Пятнадцать генов имеют
делецию / метилирование в 6 и 5 локализациях рака.
Среди них есть в регионе 3p12-3p26 (ITGA9, GORASP1,
IQSEC1, CGGBP1, NBEAL2, VHL), в пределах 3q13-
3q28 региона (PPP2R3A, FGF12, ALDH1L1, GATA2,
PLCL2). Двадцать два гена из 74 имеют изменения
только в одной локализации рака. Преобладающее
число из них (13 генов / локусов) обнаружено для рака
предстательной железы. Это может указывать на кон-
кретные механизмы канцерогенеза предстательной
железы, которые отличаются от других локализаций.
Выводы. Анализ данных NotI-микропанелей 3-й хро-
мосомы человека выявил ряд как общих генетических/
эпигенетических нарушений в семи локализациях рака,
так и опухоль-специфические изменения.
К л юч е в ы е с л ов а: NotI-микропанели, рак толстой
кишки, рак яичников, рак почки, рак легких, рак шей-
ки матки, рак молочной железы, рак предстательной
железы, гены-супрессоры роста опухолей, метилиро-
вание, делеция, хромосома 3 человека.
Received 13.04.2018
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