Korean Journal of Clinical Laboratory Science (대한임상검사과학회지)

Korean Society for Clinical Laboratory Science (대한임상검사과학회)
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Comparison of Results between Cytogenetic Technique and Molecular Genetic Technique in Colorectal Carcinoma Patients

대장암환자의 염색체 결실에서 세포유전학적 기법과 분자유전학적 기법의 결과 비교

  • Park, Cheolin (Department of Biomedical Laboratory Science, Daegu Health College) ;
  • Lee, Jae Sik (Department of Clinical Laboratory Science, Hyejeon College)
  • 박철인 (대구보건대학교 임상병리과) ;
  • 이재식 (혜전대학교 임상병리과)
  • Received : 2017.07.11
  • Accepted : 2017.08.07
  • Published : 2017.09.30
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Abstract

Globally, 1.3 million people develop colon cancer every year, and 600,000 people die each year it. In Korea, colorectal carcinoma was associated with the highest death rate, accounting for 8,380 people, among solid cancers in 2015. Among the various methods for the diagnosis and study of colorectal carcinoma, the results obtained by cytogenetic and molecular genetic methods were compared. Detection rate was 47% in 18q, 40% in 17p, 27% in 22q, and 17% in 10q via CGH; detection rate was 57% in D18S59, 50% in D18S68, 50% in TP53CA, 47% in D18S6940% in D22S274, 37% in D22S283, 27% in D10S187, and 23% in D10S541 with LOH. Microsatellite marker matching rates were 100% in D22S274, 100% in D22S283, 100% in D10S186, 100% in D10S187, 100% in D10S541, 93% in D18S69, 93% in D18S68, 92% in TP53CA, and 89% in D18S59. The agreement rate between the two methods was 94.4% based on positive results using CGH. Based on the advantages of CGH, which was the ability to obtain information regarding the entire tumor genome at once, this experiment could identify the region with significant deletion using CGH and the more limited region LOH, with a completely different approach. LOH in the recurrent high-risk group, 18q21, was helpful in the selection of treatment modalities and in prognostic estimation as well as making the most appropriate decision for treatment. Therefore, it is suggested that LOH with surgical site tissues could be one of the treatment methods for recurrent high-risk group among patients with colorectal carcinoma.

대장암은 전 세계적으로 볼 때, 매년 135만명이 발생하고 매년 60만명이 사망하는 질환으로, 한국에서도 2015년도에 8,380명이 사망하였으며, 고형 암중에서 가장 높은 증가율을 나타내고 있다. 대장암의 진단과 연구를 위한 다양한 방법 중에서 동일한 검사 샘플을 이용하여, 세포유전학적인 방법과 분자유전학적인 방법을 통해 얻어지는 결과를 비교하였다. CGH에서 결실은 18q 47%, 17p 40%, 22q 27%, 10q 17%이 나타났고, LOH는 D18S59 57%, D18S68 50%, TP53CA 50%, D18S69 47%, D22S274 40%, D22S283 37%, D10S186 27%, D10S187 27%, D10S541 23%순으로 관찰되었다. Microsatellite marker별 일치율은 D22S274 100%, D22S283 100%, D10S186 100%, D10S187 100%, D10S541 100%, D18S69 93%, D18S68 93%, TP53CA 92%, D18S59 89% 순으로 검출되었으며, CGH에서의 양성결과를 기준으로, 두 방법간의 일치율은 94.4%로 나타났다. 이번 실험은 종양 genome전체에 대한 많은 정보들을 한 번에 얻을 수 있었던 CGH의 장점을 토대로, CGH에서 의미 있게 결실을 보인 부분을, 접근 방법이 전혀 다른 LOH로 좀 더 한정된 부위의 변화를 확인할 수 있었을 뿐 아니라, 재발 고위험군인 18q21의 대립유전자의 소실을 확인하면 치료방법 선정에 도움을 줄 수 있고, 예후 추정 및 치료 결정에 유용하므로, 대장암 환자가 수술 시에는 수술 부위 조직을 이용한 LOH를 시행하여, 재발 고위험군에 대한 치료방법 선정 등 임상에서 효율적으로 활용하는 것이 필요하다고 사료된다.

Keywords

References

  1. Tariq K, Ghias K. Colorectal cancer carcinogenesis: a review of mechanisms. Cancer Biol Med. 2016;13(1):120-135. doi:10. 28092/j.issn.2095-3941.2015.0103. https://doi.org/10.20892/j.issn.2095-3941.2015.0103
  2. Viswanath B, Kim S, Lee K. Recent insights into nanotechnology development for detection and treatment of colorectal cancer. Int J Nanomedicine. 2016;2:2491-2504.
  3. Yang CY, Lu RH, Lin CH, Jen CH, Tung CY, Yang SH, et al. Single nucleotide polymorphisms associated with colorectal cancer susceptibility and loss of heterozygosity in a Taiwanese population. PLoS One. 2014;26;9(6):e100060. doi:10.1371/journal.pone.0100060.
  4. Korea National Statistical Office, KOSTAT. Statistical Yearbook of Death Statistics. Mortality by cause of death, 1990-2015 [cited 2017 August 6]. Available from: http://kostat.go.kr/wnsearch/search.jsp
  5. Henrikson NB, Webber EM, Goddard KA, Scrol A, Piper M, Williams MS, et al. Family history and the natural history of colorectal cancer: systematic review. Genet Med. 2015;17(9):702-712. https://doi.org/10.1038/gim.2014.188
  6. O'Mahoney PR, Scherl EJ, Lee SW, Milsom JW. Adenocarcinoma of the ileal pouch mucosa: case report and literature review. Int J Colorectal Dis. 2015;30(1):11-18. doi: 10.1007/s00384-014-2043-3.
  7. Sawada T, Yamamoto E, Suzuki H, Nojima M, Maruyama R, Shioi Y, et al. Association between genomic alterations and metastatic behavior of colorectal cancer identified by array-based comparative genomic hybridization. Genes Chromosomes Cancer. 2013;52(2):140-149. doi: 10.1002/gcc.22013.
  8. Zauber P, Marotta S, Sabbath-Solitare M. Copy number of the Adenomatous Polyposis coli gene is not always neutral in sporadic colorectal cancers with loss of heterozygosity for the gene. BMC Cancer. 2016;16:213. doi:10.1186/s12885-016-2243-z.
  9. Provenzale D, Jasperson K, Ahnen DJ, Aslanian H, Bray T, Gupta S, et al. Colorectal cancer screening, version 1. 2015. J Natl Compr Canc Netw. 2015;13(8):959-968. https://doi.org/10.6004/jnccn.2015.0116
  10. Shi ZZ, Zhang YM, Shang L, Hao JJ, Zhang TT, Wang BS, et al. Genomic profiling of rectal adenoma and carcinoma by array-based comparative genomic hybridization. BMC Med Genomics. 2012;5:52. https://doi.org/10.1186/1755-8794-5-52
  11. Guo T, Sun JW, Lv QP, Li XG. Allelic imbalance on chromosomes 3p, 9p and 17p in malignant progression of laryngeal mucosa. J Laryngol Otol. 2008;122(1):72-77. https://doi.org/10.1017/S002221510700761X
  12. Datta A, Dey S, Das P, Alam SK, Roychoudhury S. Transcriptome profiling identifies genes and pathways deregulated upon floxuridine treatment in colorectal cancer cells harboring GOF mutant p53. Genom Data. 2016;17(8):47-51.
  13. Laczmanska I, Karpinski P, Kozlowska J, Bebenek M, Ramsey D, Sedziak T, et al. Copy number alterations of chromosomal regions enclosing protein tyrosine phosphatase receptor-like genes in colorectal cancer. Pathol Res Pract. 2014;210(12):893-896. https://doi.org/10.1016/j.prp.2014.07.010
  14. Watanabe T, Wu TT, Catalano PJ, Ueki T, Satriano R, Haller DG, et al. Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med. 2001;344(16): 1196-1206. https://doi.org/10.1056/NEJM200104193441603
  15. Nakao K, Shibusawa M, Tsunoda A, Yoshizawa H, Murakami M, Kusano M, et al. Genetic changes in primary colorectal cancer by comparative genomic hybridization. Surg Today. 1998; 28(5):567-569. https://doi.org/10.1007/s005950050185
  16. De Angelis PM, Clausen OP, Schjolberg A, Stokke T. Chromosomal gains and losses in primary colorectal carcinomas detected by CGH and their associations with tumour DNA ploidy, genotypes and phenotypes. Br J Cancer. 1999;80(4): 526-535. https://doi.org/10.1038/sj.bjc.6690388
  17. Torabi K, Miro R, Fernandez-Jimenez N, Quintanilla I, Ramos L, Prat E, et al. Patterns of somatic uniparental disomy identify novel tumor suppressor genes in colorectal cancer. Carcinogenesis. 2015;36(10):1103-1110. https://doi.org/10.1093/carcin/bgv115
  18. Yano S, Matsuyama H, Matsuda K, Matsumoto H, Yoshihiro S, Naito K. Accuracy of an array comparative genomic hybridization (CGH) technique in detecting DNA copy number aberrations: comparison with conventional CGH and loss of heterozygosity analysis in prostate cancer. Cancer Genet Cytogenet. 2004;15;150(2):122-127. https://doi.org/10.1016/j.cancergencyto.2003.09.004
  19. Grade M, Becker H, Liersch T, Ried T, Ghadimi BM. Molecular cytogenetics: genomic imbalances in colorectal cancer and their clinical impact. Cell Oncol. 2006;28(3):71-84.
  20. Skotheim R, Diep CB, Kraggerud SM, Jakobsen KS, Lothe RA. Evaluation of loss of heterozygosity/allelic imbalance scoring in tumor DNA. Cancer Genet Cytogenet. 2001;127(1):64-70. https://doi.org/10.1016/S0165-4608(00)00433-7