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Codon 201Arg/Gly Polymorphism of DCC (Deleted in Colorectal Carcinoma) Gene in Flat- and Polypoid-Type Colorectal Tumors

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Abstract

Recent studies have identified the distinctexistence of flat-type colorectal tumors. The lowincidence of ras gene mutations in these tumors suggeststhat their genetic pathways of tumor progression may be different from those of the polypoid type.To elucidate further genetic alterations in flat-typecolorectal tumors, codon 201Arg/Glypolymorphism in the DCC (deleted in colorectalcarcinoma) gene was analyzed in normal tissue (normal colonicmucosa or peripheral lymphocytes) and in tumor tissuefrom 191 patients with colorectal tumors (36 patientswith flat-type colorectal tumors, 81 patients withpolypoid-type colorectal tumors, and 74 patients withadvanced carcinomas). For normal controls, 30 samplesobtained from patients who had neither colorectal tumors(confirmed by total colonoscopy) nor a family history of colorectal carcinoma were analyzed. DCC genecodon 201Arg/Gly polymorphism wasinvestigated by polymerase chain reaction-basedrestriction fragment length polymorphism analysis,fluorescence-based dideoxy sequencing, or both. For the flat type, thefrequency of codon 201Gly of the DCC gene was64% and 54% in the normal tissue of patients withadenoma with high-grade dysplasia and submucosalcarcinoma, respectively. It was 49%, 52%, and 49% in the normal tissueof patients with polypoid-type adenoma with high-gradedysplasia, submucosal carcinoma, and advanced carcinoma,respectively. In the normal tissue, codon 201Gly of the DCC gene was more frequentlyobserved in patients with flat-type adenoma withlow-grade dysplasia (67%) than in those withpolypoid-type adenoma with low-grade dysplasia (18%) orin normal controls (17%, P < 0.05, χ2test). Codon 201Arg/Gly polymorphism in tumortissues did not differ from that in the correspondingnormal tissues, except for 10 cases of carcinoma withloss of heterozygosity (LOH). In carcinomas with LOH, preferentialloss of the codon 201Arg allele was noted(9/10 cases). These results suggest that codon201Gly of the DCC gene is not only associatedwith flat-type colorectal tumors, but that it may serve as a usefulgenetic marker for identifying groups at higher risk forcolorectal cancer.

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REFERENCES

  1. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AMM, Bos JL: Genetic alteration during colorectal tumor development. N Engl J Med 319:525–532, 1988

    Google Scholar 

  2. Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 61:759–767, 1990

    Google Scholar 

  3. Finley GG, Schulz NT, Hill SA, Geiser JR, Pipas JM, Meisler AI: Expression of the myc gene family in different stages of human colorectal cancer. Oncogene 4:963–971, 1989

    Google Scholar 

  4. Bos JL, Fearon ER, Hamilton SR, Vries MV, van Boom JH, van Der Eb AJ, Vogelstein B: Prevarence of ras gene mutations in human colorectal cancers. Nature 327:293–297, 1987

    Google Scholar 

  5. Kinzler KW, Nilbert MC, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hamilton SR, Hedge P, Markham A, Carlson M, Joslyn G, Groden J, White R, Miki Y, Miyoshi Y, Nishisho I, Nakamura Y: Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science 251:1366–1370, 1991

    Google Scholar 

  6. Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, van Tuinen P, Ledbetter DH, Barker DF, Nakamura Y, White R, Vogelstein B: Chromosome 17 deletion and p53 gene mutations in colorectal carcinomas. Science 244:217–221, 1989

    Google Scholar 

  7. Fearon ER, Cho KR, Nigro JM, Kern SE, Simons J, Ruppert JM, Hamilton SR, Preisinger AC, Thomas G, Kinzler KW, Vogelstein B: Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247:49–56, 1990

    Google Scholar 

  8. Adachi M, Muto T, Okinaga K, Morioka Y: Clinicopathological features of the flat adenoma. Dis Colon Rectum 34:981–986, 1991

    Google Scholar 

  9. Wolber RA, Owen DA: Flat adenomas of the colon. Hum Pathol 22:70–74, 1991

    Google Scholar 

  10. Kuramoto S, Oohara T: Flat early cancers of the large intestine. Cancer 64:950–955, 1989

    Google Scholar 

  11. Ikegami M: A pathological study on colorectal cancer—from de novo carcinoma to advanced carcinoma. Acta Pathol Jpn 37:21–37, 1987

    Google Scholar 

  12. Fujimori T, Satonaka K, Yanamura-Idei Y, Nagasako K, Maeda S: Non-involvement of ras mutations in flat colorectal adenomas and carcinomas. Int J Cancer 57:51–55, 1994

    Google Scholar 

  13. Yamamura-Idei Y, Satonaka K, Fujimori T, Maeda S, Chiba T: p53 mutation in flat-and polypoid-type colorectal tumors detected by temperature gradient gel electrophoresis. Dig Dis Sci 39:2043–2048, 1994

    Google Scholar 

  14. Sasaki M, Okamoto M, Sato C, Sugio K, Soejima J, Iwama T, Ikeuchi T, Tonomura A, Miyaki M, Sasazuki T: Loss of constitutional heterozygosity in colorectal tumors from patients with familial polyposis coli and those with nonpolyposis colorectal carcinoma. Cancer Res 49:4402–4406, 1989

    Google Scholar 

  15. Miyaki M, Seki M, Okamoto M, Yamanaka A, Maeda Y, Tanaka K, Kikuchi R, Iwama T, Ikeuchi T, Tonomura A, Nakamura Y, White R, Miki Y, Utsunomiya J, Koike M: Genetic changes and histopathological types in colorectal tumors from patients with familial adenomatous polyposis. Cancer Res 50:7166–7173, 1990

    Google Scholar 

  16. Ookawa K, Sakamoto M, Hirohashi S, Yoshida Y, Sugimura T, Terada M, Kokota J: Concordant p53 and DCC alterations and allelic losses on chromosomes 13q and 14q associated with liver metastases of colorectal carcinoma. Int J Cancer 53:382–387, 1993

    Google Scholar 

  17. Iino H, Fukayama M, Maeda Y, Koike M, Mori T, Takahashi T, Kikuchi-Yanoshita R, Miyaki M, Mizuno S, Watanabe S: Molecular genetics for clinical management of colorectal carcinoma. 17p, 18q and 22q loss of heterozygosity and decreased DCC expression are correlated with metastatic potential. Cancer 73:1324–1331, 1994

    Google Scholar 

  18. Miyake S, Nagai K, Yoshino K, Oto M, Endo M, Yuasa Y: Point mutations and allelic deletion of tumor suppressor gene DCC in human esophageal squamous cell carcinomas and their relation to metastasis. Cancer Res 54:3007–3010, 1994

    Google Scholar 

  19. Cho KR, Oliner JD, Simons JW, Hedrick R, Fearon ER, Preisinger AC, Hedge P, Silvermann GA, Vogelstein B: The DCC gene; Structural analysis and mutation in colorectal carcinomas. Genomics 19:525–531, 1994

    Google Scholar 

  20. Reale MA, Hu G, Zafar AI, Getzenberg RH, Levine SM, Fearon ER: Expression and alternative splicing of the deleted in colorectal cancer (DCC) gene in normal and malignant tissues. Cancer Res 54:4493–4501, 1994

    Google Scholar 

  21. Itoh F, Hinoda Y, Ohe M, Ohe Y, Ban T, Endo T, Imai K, Yachi A: Decreased expression of DCC mRNA in human colorectal cancers. Int J Cancer 53:260–264, 1993

    Google Scholar 

  22. Ekstrand BC, Mansfield TA, Bigner SH, Fearon ER: DCC expression is altered by multiple mechanisms in brain tumours. Oncogene 11:2393–2402, 1995

    Google Scholar 

  23. Goyette MC, Cho K, Fasching CL, Levy DB, Kinzler KW, Paraskeva C, Vogelstein B, Standbridge EJ: Progression of colorectal cancer associated with multiple tumor suppressor gene defects but inhibition to tumorigenicity is accomplished by correction of any single defect via chromosome transfer. Mol Cell Biol 12:1387–1395, 1992

    Google Scholar 

  24. Narayanan R, Lawlor KL, Scaapveld RQJ, Cho KR, Vogelstein B, Tran PB-V, Osborne MP, Telang NT: Antisense RNA to putative tumor-suppressor gene DCC transforms rat-1 fibroblasts. Oncogene 7:553–561, 1992

    Google Scholar 

  25. Lawlor K, Narayanan R: Persistent expression of the tumor suppressor gene DCC is essential for neuronal differentiation. Cell Growth Differ 3:609–616, 1992

    Google Scholar 

  26. Keino-Masu K, Masu M, Hinck L, Leonardo ED, Chan SSY, Culotti G, Tessier-Lavigne M: Deleted in colorectal cancer (DCC) encodes a netrin receptor Cell 87:175–185, 1996

    Google Scholar 

  27. Hedrick L, Cho KR, Fearon ER, Wu TC, Kinzler KW, Vogelstein B: The DCC gene product in cellular differentiation and colorectal tumorigenesis. Genes Dev 8:1174–1183, 1994

    Google Scholar 

  28. Whetsell L, Maw G, Nadon N, Ringer DP, Schaefer FV: Polymerase chain reaction microanalysis of tumors from stained histological slides. Oncogene 7:2355–2361, 1992

    Google Scholar 

  29. Jiang W, Kahn SM, Guillem JG, Lu S-H, Weinstein IB: Rapid detection of ras oncogenes in human tumors: Applications to colon, esophageal, and, gastric cancer. Oncogene 4:923–928, 1989

    Google Scholar 

  30. Nagasako K, Satonaka K, Hirayama D, Fujimori T, Maeda S. A clinicopathological study on the mucosal heights of superficial type (type II) early colon cancer. Jpn J Gastroenterol 88:763, 1991 (in Japanese)

    Google Scholar 

  31. Yamagata S, Muto T, Uchida Y, Masaki T, Sawada T, Tsuno N, Hirooka T: Lower incidence of K-ras codon 12 mutation in flat colorectal adenomas than in polypoid adenomas. Jpn J Cancer Res 85:147–151, 1994

    Google Scholar 

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Authors
  1. Rieko Minami
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  2. Nobuo Aoyama
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  3. Yoichiro Honsako
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  4. Masato Kasuga
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  5. Takahiro Fujimori
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  6. Sakan Maeda
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Minami, R., Aoyama, N., Honsako, Y. et al. Codon 201Arg/Gly Polymorphism of DCC (Deleted in Colorectal Carcinoma) Gene in Flat- and Polypoid-Type Colorectal Tumors. Dig Dis Sci 42, 2446–2452 (1997). https://doi.org/10.1023/A:1018839907159

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  • DOI: https://doi.org/10.1023/A:1018839907159

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