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https://ptsldigital.ukm.my/jspui/handle/123456789/457964Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | Prof Madya Dr. Reena Rahayu Md Zin | - |
| dc.contributor.author | Nenny Noorina Binti Saaid (P53947) | - |
| dc.date.accessioned | 2023-09-13T01:48:54Z | - |
| dc.date.available | 2023-09-13T01:48:54Z | - |
| dc.date.issued | 2014-03-31 | - |
| dc.identifier.other | ukmvital:80452 | - |
| dc.identifier.uri | https://ptsldigital.ukm.my/jspui/handle/123456789/457964 | - |
| dc.description | Teknik hibridisasi genomik perbandingan ”array” (Array Comparative Genomic Hybridization-Array CGH) adalah satu teknik maju bagi menentukan kawasan yang mengalami aberasi dalam kanser. Pemetaan aberasi kromosom (amplifikasi dan delesi) dalam genom merupakan laluan penting untuk mengenalpasti gen-gen yang berperanan dalam kanser. Aberasi seperti ini akan mengubah fungsi normal gen-gen spesifik dan perubahan ini mengakibatkan kemungkinan berlakunya penambahan atau pengurangan pada pengekspresan protein. Kajian ini bertujuan untuk memeta kawasan aberasi kromosom, mengenalpasti gen-gen berpotensi yang terletak dalam kawasan aberasi tersebut dan mengkaji korelasi aberasi kromosom dengan data patologiklinikal. Array CGH dilakukan ke atas 36 sampel kanser prostat. Validasi dilakukan menggunakan teknik imunohistokimia untuk melihat pengekspresan protein bagi gengen yang terlibat. Sejumlah 1900 aberasi kromosom dikesan pada keseluruhan 36 kes dengan kes delesi (54.2%) lebih banyak dikesan berbanding kes amplifikasi (45.8%). Delesi lebih kerap dikesan pada kromosom 1p, 2q, 4q, 5q, 6q, 8p, 10q, 11q, 13q, 15q, 17q, 18q manakala amplifikasi dikesan pada kromosom 1q, 2p, 7q, 8q, 10q, 11q, 17q, 19q dan Xq. Bahagian kromosom paling kerap dikesan ialah delesi 4q25 (75%) dan amplifikasi 17q12 (86%). Gen-gen yang dikenalpasti dalam kawasan aberasi kromosom berkenaan ialah gen SYNPO2 (4q25) dan HER2 (17q12). Analisis array CGH juga mengenalpasti beberapa gen penting iaitu 5 onkogen (HER2, AR, EZH2, MYC, PSCA), 4 gen penindas tumor (SYNPO2, PTEN, NKX3-1, MXI1), 3 gen yang terlibat dalam kitar sel (CCND1, CDK10, CD9), 3 gen yang berperanan sebagai faktor transkripsi (TRPS1, TCEB1, MAP3K7) dan gen pembaikan DNA (DNA repair gene)iaitu ERCC5. Lapan belas kawasan aberasi didapati menunjukkan korelasi yang signifikan dengan umur pesakit, gred Gleason, metastasis ke bahagian tulang dan tumor berulang. Teknik imunohistokimia dijalankan ke atas dua gen yang mengalami amplifikasi (HER2 dan AR) dan dua gen yang mengalami delesi (PTEN dan NKX3-1). Tiada hubungan yang signifikan didapati antara pengekspresan protein dengan gengen berkenaan. Array CGH ialah teknik yang efektif dalam pengesanan aberasi kromosom dan boleh digabungkan dengan analisis pengekspresan untuk mengenalpasti gen-gen yang terubah dalam kanser. 4q25 dan 17q12 merupakan aberasi kromosom yang paling kerap dalam kajian ini dan gen SYNPO2 dan HER2 berkemungkinan memainkan peranan dalam tumorigenesis prostat pada pesakit Malaysia. Delesi didapati lebih kerap berbanding amplifikasi menunjukkan kehilangan fungsi gen penindas tumor ialah mekanisma penting dalam perkembangan kanser prostat. Amplifikasi dan delesi gen-gen tertentu tidak semestinya mengubah pengekpresan protein, justeru itu mekanisma atau tapakjalan lain berkemungkinan terlibat dalam pengawalaturan pengekspresan protein. Penemuan gen-gen lain dalam kajian ini dan hubungannya dengan pengekspresan protein masih perlu dijelaskan.,Array Comparative Genomic Hybridization (array CGH) is an advanced technique for determining chromosomal aberrations in cancer. Mapping the chromosomal aberrations (amplification and deletion) in the genome is an important route for the identification of genes which may play a role in cancer. Such aberrations may alter the normal function of specific genes and possibly enhance or reduce protein expression. The aims of this study were to map the aberrant regions, identify the potential genes involved in the affected regions and correlate the aberrant regions with clinicopathological parameters. Array CGH was performed on a series of 36 prostate cancer specimens. Validation by immunohistochemistry technique was done to observe the protein expression of selected genes. A total of 1900 chromosomal aberrations were detected in all 36 cases with losses (54.2%) of genetic material being more common than gains (45.8%). Chromosomal losses were frequently encountered on chromosome 1p, 2q, 4q, 5q, 6q, 8p, 10q, 11q, 13q, 15q, 17q, 18q while gains were 1q, 2p, 7q, 8q, 10q, 11q, 17q, 19q dan Xq. Loss at chromosomal region 4q25 (75%)and gain at chromosomal region 17q12 (86%) were the most frequent aberrations found in this study. Genes identified at these aberrant chromosomal regions were SYNPO2 (4q25) and HER2 (17q12). Several important genes were also detected including 5 oncogenes (HER2, AR, EZH2, MYC, PSCA), 4 tumor suppressor genes (SYNPO2, PTEN, NKX3-1, MXI1), 3 genes involved in cell cycle (CCND1, CDK10, CD9), 3 transciption factor genes (TRPS1, TCEB1, MAP3K7) and DNA repair genes (ERCC5). Eighteen aberrant chromosomal regions showed significant correlation with patient' s age, Gleason grade, bone metastasis and tumour recurrence. Immunohistochemistry technique was done on two amplified genes (HER2 and AR)and two deleted genes (PTEN and NKX3-1). No significant association found between these genes and protein expression. Array CGH is an effective technique to detect chromosomal aberrations and can be used in combination with expression analysis to identify genes altered in cancer. 4q25 and 17q12 were the most common aberrant regions found and that SYNPO2 and HER2 genes located in these regions may play a role in prostate tumorigenesis of Malaysian patients. Loss of chromosomal material in this study was more commonly observed than gains, suggesting the former is a more important mechanism in prostate tumorigenesis. Gains or losses of specific genes do not necessarily increase or reduce the protein expression, possibly due to other alternative mechanisms or pathway which might regulate protein expression. Other genes found in this study and its association with protein expression remains to be elucidated.,Master | - |
| dc.language.iso | may | - |
| dc.publisher | UKM, Kuala Lumpur | - |
| dc.relation | Faculty of Medicine / Fakulti Perubatan | - |
| dc.rights | UKM | - |
| dc.subject | Kanser prostat | - |
| dc.subject | Aberasi kromosom | - |
| dc.subject | Prostate cancer | - |
| dc.subject | Dissertations, Academic -- Malaysia | - |
| dc.title | Pengenalpastian aberasi kromosom dan gen-gen yang berpotensi dalam kanser prostat di kalangan lelaki Malaysia | - |
| dc.type | theses | - |
| dc.format.pages | 216 | - |
| Appears in Collections: | Faculty of Medicine / Fakulti Perubatan | |
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| File | Description | Size | Format | |
|---|---|---|---|---|
| ukmvital_80452+SOURCE1+SOURCE1.0.PDF Restricted Access | 4.13 MB | Adobe PDF |  View/Open |
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