Comparative Gene Analyses between Benign Prostatic Hyperplasia and Cancer Using CGH

국문 초록 (Abstract)

본 연구는 전립선종양 조직에서 9예의 암세포와 10예의 증식세포를 대상으로 comparative genomic hybridization을 이용하여 전체 유전자에 걸쳐 DNA 복제수의 변화와 위치를 밝히고자 시도하였다. 전립선 암세포와 증식세포만을 미세해부하여 proteinase K를 처리한 후 degenerate oligonucleotide primed PCR을 이용하여 유전자를 증폭시켰다. 증폭된 암조직의 DNA와 동일한 방법에 의하여 증폭된 정상 DNA에 Nick translation에 의하여 형광색소를 표지 후 정상 임파구의 중기염색체에 hybridization을 시행하여 분석한 결과 다음의 결론을 얻었다. 암세포에서 각 염색체의 gain의 빈도는 8번 염색체의 긴팔과 X 염색체에서 가장 높았으며 loss의 빈도는 8번 염색체의 짧은팔에서 가장 높았다. 증식세포에서 8번 염색체와 X 염색체의 gain은 암세포에서와 유사하게 높은 빈도로 출현하였으며 특히 8q21 근처에 대부분 집중되어 있었다. 그러나 8번 염색체의 짧은팔에서의 loss는 증식세포에서는 한 예도 관찰되지 않았다.
이상의 결과는 전립선 암세포와 증식조직의 초기 발생 관여하는 암유전자가 8q21 근처에 내재되어 있으며, 8번 염색체의 짧은팔에 암세포로의 진행에 관여하는 암 억제유전자가 있음을 시사하였다.

다국어 초록 (Multilingual Abstract)

The present study was performed to find genetic changes in both cancer and hyperplastic cells in the prostate gland, elucidating any plausible interrelations of the changes between them. Nine cases of microdissected
adenocarcinoma cells and 10 cases of microdissected hyperplastic cells in prostate tumors were analyzed to produce a map of DNA copy number changes throughout the entire genome using DOP-PCR and comparative genomic
hybridization. The chromosome number of showing copy number changes was more in cancer cells than in hyperplastic cells. Chromosome regions Xq and 8q, where near 8q21 region was highly amplified, were the most
frequent sites of gain in both cancer and hyperplastic cells. The most common region of loss in cancer cells was a chromosome region 8p (56% in frequency), followed by 16q. On the contrary, any high frequency of deletion could not be found in hyperplastic cells, contrary to the deletion in cancer cells. It is, therefore suggested that chromosome 8p deletion is a key factor toward progressing into adenocarcinoma, and that oncogene (s) near 8q21 might contribute to a common pathway to progress into both hyperplastic or precancerous and cancer cells in prostate tumor.

참고문헌 (Reference)

1 "associations between BPH and prostate cancer" 91 : 161-169, 2004

2 "allelic imbalance and fluorescence in situ hybridization on chromosome 8 in prostate cancer" comparative ge (comparative ge): 153-162, 1994

3 "Tumor suppressor genes in prostatic oncogenesis" 28-36, 1997

4 "Three distinct commonly deleted regions of chromosome arm 16q in human primary and metastatic prostate cancer" 17 : 225-233, 1996

5 "The role of the androgen receptor in the development of prostatic hyperplasia and prostate cancer" 1 89-2 101, 2003

6 "The int-2 gene product act as an epidermal growth factor in transgenic mice" 907-913, 1990

7 "The association of benign prostatic hyperplasia and cancer of the prostate" 291-301, 1992

8 "Textbook of benign prostatic hyperplasia" 1996

9 "Relationship between benign prostatic hyperplasia and cancer of the prostate" 115-20 117, 1974

10 "Mapping of regions of physical detection on chromosome 16q in prostate cancer cells by fluorescence in situ hybridization" 249-,

11 "Loss of the retinoblastoma susceptibility gene is a frequent and early event in prostate tumorigenesis" 1252-1257, 1994

12 "Loss of heterozygocity at 16q24 2 is significantly associated with metastatic and aggressive behavior of prostate cancer" 1 3356-3359, 1997

13 "High resolution of human chromosomes" 191 : 1268-1270, 1976

14 "Haploinsufficiency and reduced expression of genes localized to the 8p chromosomal region in human prostate tumors" 3 : 306-313, 2003

15 "Genetic instabilities in human cancers" 643-396 649, 1998

16 "Genetic changes in primary and recurrent prostate cancer by comparative genomic hybridization" 54 : 3824-3830, 1995

17 "Genetic alterantions in microdissected prostste cancer cells by comparative genomic hybridization" 110-114, 2000

18 "Genetic aberrations in prostate carcinoma detected by comparative genomic hybridization and microsatellite analysis association with progression and angiogenesis" 43-59 58, 2004

19 "General amplification of target DNA and a single degenerate primer" ge (ge): 718-725, 1992

20 "Fluorescence in situ hybridization analysis of 8p allelic loss and chromosome 8 instability in human prostate cancer" 3824-3830, 1994

21 "Expression of early growth response genes in human prostate cancer" 2461-2468, 1998

22 "Detection and mapping of amplified DNA sequence in breast cancer by comparative genomic hybridization" 2156-2160, 1994

23 "Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cells" 543-546, 1992

24 "Concordance rates for benign prostatic disease among twins suggest hereditary influence" 646-44 650, 1994

25 "Computer image analysis of comparative genomic hybridization" 10-19 26, 1995

26 "Clustered organization of Kruppel zinc-finger genes at Xp11 flanking a translocation breakpoint at OATL1 a physical map with locus assignments for ZNF21" ge (ge): 180-1871994

27 "Cloning and characterization of a gene that regulates cell adhesion" 529-356 532, 1992

28 "Characterization of an early growth response gene potentially involved in cell cycle regulation" which encodes a zinc finger transcription factor mol endocri (mol endocri): 1610-1620, 1995

29 "Benign prostatic hyperplasia in a transgenic mouse" 633-639, 1993