Analysis of Chromosome 8 Copy Number Changes in Colorectal Cancers by Fluorescence In Situ Hybridization (FISH).

Abstract

Objective: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Colorectal carcinogenesis has associated with the progressive acquisition of a variety of genomic alterations by neoplastic cells, some of these have been linked to early stages of CRC development. The aims of this study (1) to identify alterations of chromosome 8 in primary colorectal carcinomas from Turkish patients and (2) to determine which alterations of chromosome 8 are early events during the development of colorectal carcinoma using fluorescence in situ hybridization (FISH). Materials and Methods: To reveal the significance of genetic abnormalities of the chromosome 8, 28 colorectal tumors were analyzed using FISH. The centromeric-probe for chromosome 8 was used for FISH. In each case, at least 200 nuclei were scored for each hybridization. Results: Monosomy in 3.6%, disomy in 39.3%, trisomy in 53.6% and tetrasomy in 3.6% of the analyzed adenomas were determined. Chromosome 8 gain was found in 5 of 8 (62.5%) nonpolypoid and 3of 9 (33.3%) polypoid cancers. There was statistically significant correlation between chromosome 8 gain and stage of CRC. Conclusions: There are several reports of chromosome 8 gain in solid tumors. FISH is a useful method to detect genetic abnormalities in solid tumors. It was shown that chromosome 8 gain FISH associated with the stage of CRC. Chromosome 8 monosomy may be a early event in CRC. Further studies involving more patients need to determine the importance of this alteration in CRC. ©2007, Firat University, Medical Faculty

Keywords

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Kolorektal Kanserlerde Floresans in situ Hibridizasyon (FISH) Kullanılarak Kromozom 8 Kopya Sayı Değişimlerinin Analizi

Abstract

Amaç: Kolorektal kanser (KRK) dünyadaki en yaygın malignansilerden biridir. Kolorektal karsinogenezis neoplastik hücrelerde meydana gelen çeşitli genetik değişikliklerin birikimiyle beraberlik göstermektedir. Bunlardan bazıları KRK gelişiminin erken safhalarında gerçekleşmektedir. Bu çalışmanın amacı, Floresans in situ Hibridizasyon (FISH) kullanılarak Türk primer kolorektal kanserli hastalarda kromozom 8 değişimlerini tanımlamak ve kromozom 8 değişimlerinin kolorektal kanserin gelişiminde erken bir olay olup olmadığını tespit etmektir. Gereç ve Yöntem: Kromozom 8'in genetik anomalilerinin anlamını göstermek için 28 kolorektal kanser FISH'le analiz edildi. FISH için kromozom 8 sentromerik prob kullanıldı. Her bir hasta için en azından 200 hücredeki sinyaller incelendi. Bulgular: Analiz edilen tümörlerin %3.6'sında monozomi, %39.3'ünde dizomi, %53.6'sında trizomi ve %3.6'sında tetrazomi saptandı. Kromozom 8 kazancı 8 nonpolipoid kanserin 5'inde (%62.5) ve 9 nonpolipoid kanserin 3'ünde (%33.3)'de bulundu. Kromozom 8 kazancı ve KRK evresi arasında istatistiki olarak anlamlı korelasyon vardı. Sonuç: Solit tümörlerde kromozom 8 kazancıyla ilgili birkaç çalışma vardır. FISH solit tümörlerdeki genetik anomalilerin tespiti için faydalı bir yöntemdir. Kromozom 8 kazancı ve KRK evresi arasında ilişki olduğu gösterildi. Kromozom 8 monozomisi KRK'da erken bir olay olabilir. Bu değişimin öneminin ortaya konması için KRK'da daha fazla hasta sayısı içeren çalışmaların yapılması gerekmektedir. ©2007, Fırat Üniversitesi, Tıp Fakültesi

Keywords

• Kolorektal kanser, floresans in situ hibridizasyon, kromozom 8

References

1. Leslie A, Carey FA, Pratt NR, Steele RJC. The colorectal adenoma-carcinoma sequence. British Journal of Surgery 2002; 89: 845-860.
2. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 61: 759-67
3. Markowitz S. DNA repair defects inactivate tumor suppressor genes and induce hereditary and sporadic colon cancers. J Clin Oncol 2000; 18: 75-80.
4. Nowell PC. The clonal evolution of tumor cell populations. Science 1976; 194: 23-8.
5. Bayani J, Squire JA. Spectral karyotyping. Methods Mol Biol 2002; 204: 85-104.
6. Atkin NB, Baker MC. Numerical chromosome changes in 165 malignant tumors. Evidence for a nonrandom distribution of normal chromosomes. Cancer Genet Cytogenet 1991; 52: 113- 121.
7. Cajulis RS, Frias-Hidvegi D. Detection of numerical chromosomal abnormalities in malignant cells in fine needle aspirates by fluorescence in situ hybridization of interphase cell nuclei with chromosome-specific probes. Acta Cytol 1993; 37: 391-396.
8. Field JK, Spandidos DA. The role of ras and myc oncogenes in human solid tumours and their relevance in diagnosis and prognosis (review). Anticancer Res 1990; 10: 1-22.

9. Visscher DW, Wallis T, Awussah S, et al. Evaluation of MYC and chromosome 8 copy number in breast carcinoma by interphase cytogenetics. Genes Chromosomes Cancer 1997; 18: 1-7.
10. Adachi P, Camparoto M, Sakamoto-Hojo E, et al. Fluorescent in situ hybridization in liver cell touch preparations from autopsy. . Pathol Res Pract 2005; 1: 41-47.
11. Di Vinci A, Infusini E, Peveri C, et al. Deletions at chromosome 1p by fluorescence in situ hybridization are an early event in human colorectal tumorigenesis. Gastroenterology. 1996; 111: 102-107.
12. Di Vinci A, Infusini E, Peveri C, et al. Correlation between 1p deletions and aneusomy in human colorectal adenomas. Int J Cancer 1998; 75: 45-50.
13. Takahashi Y, Shintaku K, Ishii Y, et al. Analysis of Myc and chromsome 8 copy number changes in gastrointestinal cancers by dual-color fluorescence in situ hybridization. Cancer Genetics and Cytogenetics 1998; 107: 61-64.
14. Aragane H, Sakakura C, Nakanishi M, et al. Chromosomal aberration in colorectal cancers and liver metastases analyzed by comparative genomic hybridization. International Journal of Cancer 2001; 94: 623-629.
15. He OJ, Zeng WF, Sham JST, et al. Recurrent genetic alterations in 26 colorectal carcinomas and 21 adenomas from Chinese patients. Cancer Genetics and Cytogenetics 2003; 144:112-118.
16. Nakao K, Mehta KR, Fridlyand J, et al. High-resolution analysis of DNA copy number alterations in colorectal cancer by array- based comparative genomic hybridization. Carcinogenesis 2004; 25: 1345-57.
17. Pirc-Danoewinata H, Bull JP, Okamoto I, et al. Cytogenetic findings in colorectal cancer mirror multistep evoluation of colorectal cancer. Wiener Klinische Wochenschrift 1996; 23: 752-758.
18. Sandberg AA, The chromosomes in human cancer and leukemia. 2, Elsevier Science Publishing Co., New York, 1990; 738-739.
19. Giaretti W. Aneuploidy mechanisms in human colorectal preneoplastic lesions and Barrett's esophagus. Is there a role for K-ras and p53 mutations? Anal Cell Pathol 1997;15: 99-117.
20. Richter H, Slezak P, Walch A, et al. Distinct chromosomal imbalances in nonpolypoid and polypoid colorectal adenomas indicate different genetic pathways in the development of colorectal neoplasms. American Journal of Pathology 2003; 163: 287-294.
21. Kabul Tarihi: 28.11.2006