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Array Comparative Genomic Hybridization Analysis Identified The Chromosomal Aberrations and Putative Genes Involved in Prostate Tumorigenesis of Malaysian Men (Analisis Tatasusunan Perbandingan Genom Penghibridan dalam
Mengenal Pasti Aberasi Kromosom dan Gen Berkemungkinan Terlibat dalam
Tumorigenesis Prostat dalam Kalangan Lelaki di Malaysia)
NENNY NOORINA SAAID1, REENA RAHAYU MD ZIN1*, SITI AISHAH MD ALI1,
SHARIFAH NOOR AKMAL SYED HUSSAIN1, ZULKIFLI ZAINUDDIN2 & ZUBAIDAH ZAKARIA3
1Department
of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical
Centre
56000 Kuala Lumpur, Malaysia
2Department of
Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre
56000 Kuala Lumpur, Malaysia
3Hematology Units,
Cancer Research Centre, Institute for Medical Research
56000 Kuala Lumpur, Malaysia
Diserahkan:
31 Julai 2013/Diterima: 9 Januari 2014
ABSTRACT
The
identification of chromosomal aberrations in prostate cancer has been widely
studied with several known oncogenes and tumor suppressor genes have
successfully been discovered. The most frequent aberrations detected in western
population were losses in chromosome 5q, 6q, 8p, 13q, 16q, 17p, 18q and gains
of 7p/q and 8q. The purpose of this study was to determine the chromosomal
aberrations among Malaysian men of Southeast Asia population and discover those
potential genes within that chromosomal aberrant region. Thirty-six
formalin-fixed paraffin embedded specimens consist of eight organ-confined
prostate cancer cases, five with capsular invasion, 14 showed metastasis and
nine cases had no tumor stage recorded, were analyzed by array CGH technique. Chromosomal losses were frequently detected at 4q, 6q,
8p, 13q, 18q while gains at 7q, 11q, 12p, 16q and 17q. Gain of 16q24.3 was
statistically significant with tumor size. Gains of 6q25.1 and Xq12 as well as
losses of 3p13-p1.2 and 13q33.1-q33.3 were significantly correlated with
Gleason grade whereas 12p13.31 gain was associated with bone metastasis.
Several potential genes have also been found within that aberrant region which
is myopodin (4q26-q27), ROBO1 (3p13-p11.2), ERCC5 (13q33.1-q33.3) and CD9 (12p13.31), suggesting
that these genes may play a role in prostate cancer progression. The
chromosomal aberrations identified by array CGH analysis could provide important clues to discover potential
genes associated with prostate tumorigenesis of Malaysian men.
Keywords:
Array CGH; chromosomal
aberrations; prostate cancer; putative genes
ABSTRAK
Pengenalpastian
aberasi kromosom dalam kanser prostat telah dikaji secara meluas dengan
beberapa onkogen dan gen penindas tumor telah berjaya ditemui. Aberasi kromosom
yang paling kerap dikesan dalam kalangan penduduk barat ialah delesi pada
kromosom 5q, 6q, 8p, 13q, 16q, 17p, 18q dan amplifikasi pada kromosom 7p/q dan
8q. Tujuan kajian ini adalah untuk menentukan aberasi kromosom dalam kalangan
lelaki Malaysia di Asia Tenggara dan seterusnya mengenal pasti gen berpotensi
yang terkandung dalam kawasan kromosom yang mengalami aberasi. Sejumlah 36 blok
tisu spesimen kanser prostat yang diawet formalin dan terbenam dalam lilin
parafin, digunakan dalam kajian ini yang terdiri daripada 8 kes organ-terbatas
kanser prostat, 5 kes dengan kapsular invasif, 14 kes menunjukkan metastasis
manakala 9 kes tiada rekod peringkat tumor. Sampel dianalisis oleh teknik penghibridan
perbandingan genomik tatasusunan. Delesi kromosom lebih kerap dikesan pada 5q,
6q, 8p, 13q, 18q manakala amplifikasi pada 7q, 11q, 12p, 16q dan 17q.
Amplifikasi 16q24.3 menunjukkan hubungan yang signifikan dengan saiz tumor.
Amplifikasi 6q25.1 dan Xq12 serta delesi 3p13-p1.2 dan 13q33.1-q33.3 adalah
signifikan dengan gred tumor manakala amplifikasi 12p13.31 adalah signifikan
dengan metastasis ke bahagian tulang. Beberapa gen yang berpotensi juga telah
ditemui di dalam kawasan aberasi berkenaan termasuklah gen myopodin (4q26-S27), ROBO1 (3p13-p11.2), ERCC5 (13q33.1-q33.3) dan CD9 (12p13.31) yang
berkemungkinan berperanan penting dalam perkembangan kanser prostat. Aberasi
kromosom yang dikesan oleh teknik tatasusunan CGH memberi petunjuk penting terhadap penemuan gen berpotensi yang
berkemungkinan terlibat dalam tumorigenesis prostat pesakit Malaysia.
Kata kunci: Aberasi kromosom; gen yang berkemungkinan; kanser
prostat; tatasusunan CGH
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*Pengarang untuk surat-menyurat; email: reenarahayu@ppukm.ukm.edu. my
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