Loss of Heterozygosity on Chromosome 15q15 Near Thrombospondin-1 Gene in Breast Carcinomas
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Background : Chromosome 15q15 near the thrombospondin-1 (THBS-1) gene may be associated with tumor progression and metastasis. To clarify the potential role of the15q15 region in progression of breast carcinoma, we investigated the loss of heterozygosity (LOH) and the microsatellite instability (MSI) status of chromosome 15q15. Methods : LOH and MSI were detected in 84 breast carcinoma specimens using PCR-based microsatellite analysis with three microsatellite markers. Results : Of 77 breast carcinomas containing the heterozygous alleles, 25 (32%) showed LOH in at least one microsatellite marker. Partial LOH and total LOH were detected in 14 (18.27%) and 11 (14.3%) cases. The total LOH were inversely correlated with node metastasis. A single LOH at D15S514 was inversely correlated with nuclear grade and a single LOH at the D15S129 allele was associated with increased expression of the THBS- 1 gene. MSI-positive breast carcinomas detected in 14 (17%) cases showed no correlation with any clinicopathologic feature. Conclusions : These results indicate that loss of the chromosome 15q15 region delays the progression of breast carcinoma because the magnitude of LOH is large and involves the THBS-1 gene and additional genetic elements. The genes located on chromosome 15q15 probably play a tissue-type-dependent role in malignant growth of the tumor.
Abstract
Background : Chromosome 15q15 near the thrombospondin-1 (THBS-1) gene may be associated with tumor progression and metastasis. To clarify the potential role of the15q15 region in progression of breast carcinoma, we investigated the loss of heterozygosity (LOH) and the microsatellite instability (MSI) status of chromosome 15q15. Methods : LOH and MSI were detected in 84 breast carcinoma specimens using PCR-based microsatellite analysis with three microsatellite markers. Results : Of 77 breast carcinomas containing the heterozygous alleles, 25 (32%) showed LOH in at least one microsatellite marker. Partial LOH and total LOH were detected in 14 (18.27%) and 11 (14.3%) cases. The total LOH were inversely correlated with node metastasis. A single LOH at D15S514 was inversely correlated with nuclear grade and a single LOH at the D15S129 allele was associated with increased expression of the THBS- 1 gene. MSI-positive breast carcinomas detected in 14 (17%) cases showed no correlation with any clinicopathologic feature. Conclusions : These results indicate that loss of the chromosome 15q15 region delays the progression of breast carcinoma because the magnitude of LOH is large and involves the THBS-1 gene and additional genetic elements. The genes located on chromosome 15q15 probably play a tissue-type-dependent role in malignant growth of the tumor.
참고문헌 (30)
- Fearon ER, "A genetic model for colorectal tumorigenesis", Cell, 61, pp.759~767 (1990)
- Wick W, "Evidence for a novel tumor suppressor gene on chromosome 15 associated with progression to a metastatic stage in breast cancer", Oncogene, 12, pp.973~978 (1996)
- Caduff RF, "Clinical and pathological significance of microsatellite instability in sporadic endometrial carcinoma", Am J Pathol, 148, pp.1671~1678 (1996)
- Choi SW, "Genetic classification of colorectal cancer based on chromosomal loss and microsatellite instability predicts survival", Clin Cancer Res, 8, pp.2311~2322 (2002)
- Rhyu MG, "Microsatellite instability occurs frequently in human gastric carcinoma", Oncogene, 9, pp.29~32 (1994)
- Mironov NM, "Alterations of (CA)n DNA repeats and tumor suppressor genes in human gastric cancer", Cancer Res, 54, pp.41~44 (1994)
- Risinger JI, "Genetic instability of microsatellites in endometrial carcinoma", Cancer Res, 53, pp.5100~5103 (1993)
- Shridhar V, "Genetic instability of microsatellite sequences in many non-small cell lung carcinomas", Cancer Res, 54, pp.2084~2087 (1994)
- Yee CJ, "Microsatellite instability and loss of heterozygosity in breast cancer", Cancer Res, 54, pp.1641~1644 (1994)
- Kim KM, "Genetic classification of intestinal-type and diffuse-type gastric cancers based on chromosomal loss and microsatellite instability", Virchows Arch, 443, pp.491~500 (2003)
- Chen LC, "Heterogeneity for allelic loss in human breast cancer", J Natl Cancer Inst, 84, pp.506~510 (1992)
- Miller BJ, "Pooled analysis of loss of heterozygosity in breast cancer: a genome scan provides comparative evidence for multiple tumor suppressors and identifies novel candidate regions", Am J Hum Genet, 73, pp.748~767 (2003)
- Girard L, "Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer, and loci clustering", Cancer Res, 60, pp.4894~4906 (2000)
- De Rienzo A, "Loss of heterozygosity analysis defines a 3-cM region of 15q commonly deleted in human malignant mesothelioma", Oncogene, 20, pp.6245~6249 (2001)
- Park WS, "A distinct tumor suppressor gene locus on chromosome 15q21.1 in sporadic form of colorectal cancer", Cancer Res, 60, pp.70~73 (2000)
- Pa@ez G, "Loss of heterozygosity (LOH) in 15q26.2→ ter in breast cancer", Mutat Res, 484, pp.103~106 (2001)
- Adams JC, "The thrombospondins", Int J Biochem Cell Biol, 36, pp.961~968 (2004)
- Weinstat-Saslow DL, "Transfection of thrombospondin 1 complementary DNA into a human breast carcinoma cell line reduces primary tumor growth, metastatic potential, and angiogenesis", Cancer Res, 54, pp.6504~6511 (1994)
- Wang-Rodriguez J, "Elevated osteopontin and thrombospondin expression identifies malignant human breast carcinoma but is not indicative of metastatic status", Breast Cancer Res, 5, pp.R136~R143 (2003)
- Lee JY, "A simple, precise and economical microdissection technique for analysis of genomic DNA from archival tissue sections", Virchows Arch, 433, pp.305~309 (1998)
- 김세훈, "한국인 희소돌기아교세포종의 1p", 19q 이형접합소실 검사에 적합한 현미부수체 표지자, 2005, pp.39(1), 23~33[DOI]
- Cho HA, "Genetic Classification of Breast Cancer based on Unilateral Chromosomal Loss", J Korean Breast Cancer Soc, 7, pp.217~227 (2004)
- Liu B, "hMSH2 mutations in hereditary nonpolyposis colorectal cancer kindreds", Cancer Res, 54, pp.4590~4594 (1994)
- Burks RT, "Microsatellite instability in endometrial carcinoma", Oncogene, 9, pp.1163~1166 (1994)
- Halford SE, "MSI-low, a real phenomenon which varies in frequency among cancer types", J Pathol, 201, pp.389~394 (2003)
- Inoue Y, "Genomic instability and tissue expression of angiogenic growth factors in sporadic colorectal cancer", Surgery, 139, pp.305~311 (2006)
- Rhiem K, "Chromosomal region 15q21.1 is a frequent target of allelic imbalance in advanced breast carcinomas", Int J Cancer, 106, pp.74~77 (2003)
- Jaffe E, "Mapping of the thrombospondin gene to human chromosome 15 and mouse chromosome 2 by in situ hybridization", Genomics, 7, pp.123~126 (1990)
- Maacke H, "Over-expression of wild-type Rad51 correlates with histological grading of invasive ductal breast cancer", Int J Cancer, 88, pp.907~913 (2000)
- Rapakko K, "Screening for RAD51 and BRCA2 BRC repeat mutations in breast and ovarian cancer families", Cancer Lett, 236, pp.142~147 (2006)