dcc genes

Summary

Summary: Tumor suppressor genes located in the 18q21-qter region of human chromosome 18. The absence of these genes is associated with the formation of colorectal cancer (DCC stands for deleted in colorectal cancer). The products of these genes show significant homology to neural cell adhesion molecules and other related cell surface glycoproteins.

Top Publications

  1. Suh J, Lim S, Kim J, Hong S, Kang G. Comparison of clinicopathologic characteristics and genetic alterations between microsatellite instability-positive and microsatellite instability-negative sporadic colorectal carcinomas in patients younger than 40 years old. Dis Colon Rectum. 2002;45:219-28 pubmed
  2. Fazeli A, Dickinson S, Hermiston M, Tighe R, Steen R, Small C, et al. Phenotype of mice lacking functional Deleted in colorectal cancer (Dcc) gene. Nature. 1997;386:796-804 pubmed
    ..These observations fail to support a tumour-suppressor function for Dcc, but are consistent with the hypothesis that DCC is a component of a receptor for netrin-1. ..
  3. Liu J, Yao F, Wu R, Morgan M, Thorburn A, Finley R, et al. Mediation of the DCC apoptotic signal by DIP13 alpha. J Biol Chem. 2002;277:26281-5 pubmed
    ..Inhibition of endogenous DIP13 alpha expression by small interfering RNA blocks DCC-induced apoptosis. Our data suggest that DIP13 alpha is a mediator of the DCC apoptotic pathway. ..
  4. Cho K, Oliner J, Simons J, Hedrick L, Fearon E, Preisinger A, et al. The DCC gene: structural analysis and mutations in colorectal carcinomas. Genomics. 1994;19:525-31 pubmed
    ..A second tumor with a point mutation in intron 13 was also found. The regional map and genomic structure of DCC should provide the means to more extensively study DCC gene alterations and protein function in normal and neoplastic cells. ..
  5. Patterson H, Gill S, Fisher C, Law M, Jayatilake H, Fletcher C, et al. Abnormalities of the p53 MDM2 and DCC genes in human leiomyosarcomas. Br J Cancer. 1994;69:1052-8 pubmed
    ..Except for evidence of a rearrangement in a single leiomyosarcoma cell line, SK-UT-1, we have found no direct evidence to support a role for mutation of the gene in the development of human soft-tissue tumours. ..
  6. Zauber N, Wang C, Lee P, Redondo T, Bishop D, Goel A. Ki-ras gene mutations, LOH of the APC and DCC genes, and microsatellite instability in primary colorectal carcinoma are not associated with micrometastases in pericolonic lymph nodes or with patients' survival. J Clin Pathol. 2004;57:938-42 pubmed
    ..Micrometastases do not provide prognostic information on survival. There is value in increasing the numbers of lymph nodes removed and analysed along with the primary tumour. ..
  7. Kato H, Zhou Y, Asanoma K, Kondo H, Yoshikawa Y, Watanabe K, et al. Suppressed tumorigenicity of human endometrial cancer cells by the restored expression of the DCC gene. Br J Cancer. 2000;82:459-66 pubmed
    ..These observations imply a role of DCC in regulation of normal endometrial cell growth, and categorize DCC as the tumour suppressor gene for endometrial cancer. ..
  8. Carvalho A, Chuang A, Jiang W, Lee J, Begum S, Poeta L, et al. Deleted in colorectal cancer is a putative conditional tumor-suppressor gene inactivated by promoter hypermethylation in head and neck squamous cell carcinoma. Cancer Res. 2006;66:9401-7 pubmed
    ..These results suggest that DCC is a putative conditional tumor-suppressor gene that is epigenetically inactivated by promoter hypermethylation in a majority of HNSCC. ..
  9. Mehlen P, Rabizadeh S, Snipas S, Assa Munt N, Salvesen G, Bredesen D. The DCC gene product induces apoptosis by a mechanism requiring receptor proteolysis. Nature. 1998;395:801-4 pubmed

More Information

Publications62

  1. Saw R, Morgan M, Koorey D, Painter D, Findlay M, Stevens G, et al. p53, deleted in colorectal cancer gene, and thymidylate synthase as predictors of histopathologic response and survival in low, locally advanced rectal cancer treated with preoperative adjuvant therapy. Dis Colon Rectum. 2003;46:192-202 pubmed
    ..Thymidylate synthase immunohistochemistry appears to be the most promising factor of those assessed in predicting tumor down-staging after preoperative chemoradiotherapy for locally advanced low rectal cancers. ..
  2. Yamaguchi A. [Genetic changes in liver metastasis of colorectal cancer and their clinical application]. Nihon Geka Gakkai Zasshi. 2001;102:370-5 pubmed
    ..These adhesion molecules may be a biological marker of liver metastasis. In addition, treatment targeting these genes will be a potent therapy for liver metastasis in the future. ..
  3. Dahlsveen I, Gilfillan G, Shelest V, Lamm R, Becker P. Targeting determinants of dosage compensation in Drosophila. PLoS Genet. 2006;2:e5 pubmed
    ..Our bioinformatics analysis suggests that DCC binding sites may be composed of variable combinations of degenerate motifs. ..
  4. Yoshiya G, Takahata T, Hanada N, Suzuki K, Ishiguro A, Saito M, et al. Influence of cancer-related gene polymorphisms on clinicopathological features in colorectal cancer. J Gastroenterol Hepatol. 2008;23:948-53 pubmed publisher
    ..From these preliminary data, these polymorphisms would be candidates predicting the clinicopathological features of colorectal cancer, but further more systematic gene analyses are warranted. ..
  5. Killian A, Di Fiore F, Le Pessot F, Blanchard F, Lamy A, Raux G, et al. A simple method for the routine detection of somatic quantitative genetic alterations in colorectal cancer. Gastroenterology. 2007;132:645-53 pubmed
    ..Its flexibility will allow the integration of clinically relevant genes. This high throughput method should be a valuable complementary tool of fluorescent in situ hybridization and comparative genomic hybridization. ..
  6. Baisse B, Bouzourene H, Saraga E, Bosman F, Benhattar J. Intratumor genetic heterogeneity in advanced human colorectal adenocarcinoma. Int J Cancer. 2001;93:346-52 pubmed
    ..Taking into account such a significant genetic heterogeneity of colorectal tumors, the use of genetic markers for prognosis management should be reconsidered. ..
  7. Fowler M, Fowler J, Ducatman B, Barnes L, Hunt J. Malignant mixed tumors of the salivary gland: a study of loss of heterozygosity in tumor suppressor genes. Mod Pathol. 2006;19:350-5 pubmed
    ..Furthermore, these data support prior studies that suggest a common clonal origin for the benign and malignant components of carcinomas ex pleomorphic adenoma...
  8. Suto T, Sugai T, Habano W, Uesugi N, Kanno S, Saito K, et al. Allelotype analysis of the PTEN, Smad4 and DCC genes in biliary tract cancer. Anticancer Res. 2002;22:1529-36 pubmed
    Aberrations of the PTEN, Smad4 and DCC genes have not been determined in biliary tract cancers. We performed allelotype analysis to screen for alterations of these genes...
  9. Terdiman J, Aust D, Chang C, Willenbucher R, Baretton G, Waldman F. High resolution analysis of chromosome 18 alterations in ulcerative colitis-related colorectal cancer. Cancer Genet Cytogenet. 2002;136:129-37 pubmed
    ..SMAD2 was retained in four tumors having loss of SMAD4 and DCC. Loss of SMAD4 alone was seen in one tumor. The present data indicate that the loss of SMAD4 and DCC occurs in the majority of colitis-related cancers. ..
  10. Zauber N, Marotta S, Berman E, Grann A, Rao M, Komati N, et al. Molecular genetic changes associated with colorectal carcinogenesis are not prognostic for tumor regression following preoperative chemoradiation of rectal carcinoma. Int J Radiat Oncol Biol Phys. 2009;74:472-6 pubmed publisher
    ..We assessed a series of rectal cancers for the molecular changes of loss of heterozygosity of the APC and DCC genes, K-ras mutations, and microsatellite instability, changes that have clearly been associated with rectal ..
  11. Wang M, Lu R, Fang D. [The possible role of loss of heterozygosity at APC, MCC and DCC genetic loci in esophageal carcinoma]. Zhonghua Zhong Liu Za Zhi. 1999;21:16-8 pubmed
    To investigate the alterations of APC, MCC and DCC genes in human esophageal carcinoma...
  12. Srour M, Rivière J, Pham J, Dube M, Girard S, Morin S, et al. Mutations in DCC cause congenital mirror movements. Science. 2010;328:592 pubmed publisher
    ..Functional analysis of the mutant DCC protein from the French Canadian family revealed a defect in netrin-1 binding. Thus, DCC has an important role in lateralization of the human nervous system. ..
  13. Fujita M, Enomoto T, Murata Y. Genetic alterations in ovarian carcinoma: with specific reference to histological subtypes. Mol Cell Endocrinol. 2003;202:97-9 pubmed
    ..Although inactivation of p16 by point mutation or deletion is rare, p16 inactivation by loss of expression is relatively common. ..
  14. Cong W, Zhang S, Xian Z, Wu W, Wu M. [Study on loss of heterozygosity and microsatellite instability in hepatocellular carcinoma]. Zhonghua Bing Li Xue Za Zhi. 2005;34:71-4 pubmed
    ..On the other hand, MCC gene seems to play no role in the whole process. ..
  15. Jessup J, Loda M. Prognostic markers in rectal carcinoma. Semin Surg Oncol. 1998;15:131-40 pubmed
  16. Wagner J. Technology evaluation: tgDCC-E1A, targeted genetics/MD Anderson. Curr Opin Mol Ther. 1999;1:266-70 pubmed
    ..These three patents provide the company with broad patent protection for tgDCC-E1A and all future products based on the use of the E1A or LT gene as tumor suppressors [259808]. ..
  17. Houlston R. What we could do now: molecular pathology of colorectal cancer. Mol Pathol. 2001;54:206-14 pubmed
  18. Hadziavdić V, Pavlovic Calic N, Eminovic I. Microsatellite instability and loss of heterozygosity of tumor suppressor genes in Bosnian patients with sporadic colorectal cancer. Bosn J Basic Med Sci. 2008;8:313-21 pubmed
    ..These changes result in MMR inactivation, which causes RER+ phenotype. Our results suggest a connection between alteration in some tumor suppressor genes and MSI phenotype of sporadic colorectal cancer in Bosnian population. ..
  19. Liang J, Huang K, Cheng A, Jeng Y, Wu M, Wang S. Clinicopathological and molecular biological features of colorectal cancer in patients less than 40 years of age. Br J Surg. 2003;90:205-14 pubmed
    ..The mechanisms underlying the inconsistency between the presence of MSI-H and a family history of cancer in these early-onset colorectal cancers deserve further investigation. ..
  20. Cong W, Bakker A, Swalsky P, Raja S, Woods J, Thomas S, et al. Multiple genetic alterations involved in the tumorigenesis of human cholangiocarcinoma: a molecular genetic and clinicopathological study. J Cancer Res Clin Oncol. 2001;127:187-92 pubmed
  21. Mattar R, Nonogaki S, Silva C, Alves V, Gama Rodrigues J. P53 and Rb tumor suppressor gene alterations in gastric cancer. Rev Hosp Clin Fac Med Sao Paulo. 2004;59:172-80 pubmed
    ..The p53 gene was affected in both intestinal and diffuse histological types of gastric cancer. ..
  22. Parent A, Barnes N, Taniguchi Y, Thinakaran G, Sisodia S. Presenilin attenuates receptor-mediated signaling and synaptic function. J Neurosci. 2005;25:1540-9 pubmed
  23. Sato K, Tamura G, Tsuchiya T, Endoh Y, Usuba O, Kimura W, et al. Frequent loss of expression without sequence mutations of the DCC gene in primary gastric cancer. Br J Cancer. 2001;85:199-203 pubmed
    ..01). These results indicate that DCC is frequently silenced, probably by epigenetic mechanisms instead of sequence mutations in gastric cancer. ..
  24. Gad J, Keeling S, Wilks A, Tan S, Cooper H. The expression patterns of guidance receptors, DCC and Neogenin, are spatially and temporally distinct throughout mouse embryogenesis. Dev Biol. 1997;192:258-73 pubmed
    ..In summary, these observations indicate that Neogenin is the predominant member of this subfamily in mesodermal tissues, while DCC and Neogenin may play complementary roles in the generation of the fully functional CNS. ..
  25. Kolodziej P. DCC's function takes shape in the nervous system. Curr Opin Genet Dev. 1997;7:87-92 pubmed
    ..Netrins and their DCC-related receptors thus play an evolutionarily conserved role in midline guidance, and DCC may be required more generally for cellular morphogenesis. ..
  26. Kim H, Jeon S, Kang J, Kim M, Ko H, Jung J, et al. Expression of DCC in differentiating ameloblasts from developing tooth germs in rats. Arch Oral Biol. 2009;54:563-9 pubmed publisher
    ..This study examined the expression pattern of the Deleted-in-colorectal-carcinoma (DCC) gene in developing rat tooth germs...
  27. Cunningham C, Dunlop M, Bird C, Wyllie A. Deletion analysis of chromosome 8p in sporadic colorectal adenomas. Br J Cancer. 1994;70:18-20 pubmed
    ..It is concluded that the chromosome 8p locus is involved preferentially in the development of carcinomas rather than adenomas. ..
  28. Lee G, Kim Y, Kim J, Kim M, Shin K, Won Y, et al. Characterization of novel cell lines established from three human oral squamous cell carcinomas. Int J Oncol. 2002;20:1151-9 pubmed
    ..These well-characterized human OSCC cell lines should serve as useful tools for understanding the biological characteristics of oral cancer. ..
  29. Hall R, Merriman M, Green R, Markham V, Smyth D, Heward J, et al. The deleted in colorectal carcinoma (DCC) gene 201 R --> G polymorphism: no evidence for genetic association with autoimmune disease. Eur J Hum Genet. 2003;11:840-4 pubmed
    ..Thus, the DCC 201 R --> G polymorphism does not appreciably influence risk of developing the autoimmune diseases tested. ..
  30. Shi M, Zheng M, Liu Z, Hu Z, Huang Y, Chen J, et al. DCC is specifically required for the survival of retinal ganglion and displaced amacrine cells in the developing mouse retina. Dev Biol. 2010;348:87-96 pubmed publisher
    ..Thus, our findings suggest that DCC is a key regulator for the survival of specific types of neurons during retinal development and that DCC-P3 domain is essential for this developing event. ..
  31. 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. 1994;54:3007-10 pubmed
    ..These results indicate that alterations of the DCC gene are related to the degree of lymph node metastasis and the degree of differentiation. ..
  32. Emilion G, Langdon J, Speight P, Partridge M. Frequent gene deletions in potentially malignant oral lesions. Br J Cancer. 1996;73:809-13 pubmed
    ..This type of molecular profiling may help to identify patients with lesions that may recur or acquire additional genetic events and progress to malignancy...
  33. Maesawa C, Tamura G, Suzuki Y, Ogasawara S, Sakata K, Kashiwaba M, et al. The sequential accumulation of genetic alterations characteristic of the colorectal adenoma-carcinoma sequence does not occur between gastric adenoma and adenocarcinoma. J Pathol. 1995;176:249-58 pubmed
    ..Alterations of the p53 and DCC genes occurred frequently both in differentiated and in undifferentiated gastric carcinomas...
  34. Woodford Richens K, Rowan A, Gorman P, Halford S, Bicknell D, Wasan H, et al. SMAD4 mutations in colorectal cancer probably occur before chromosomal instability, but after divergence of the microsatellite instability pathway. Proc Natl Acad Sci U S A. 2001;98:9719-23 pubmed
    ..Thus, MSI(+) cancers may diverge first, followed by CIN(+) (chromosomal instability) cancers, leaving other cancers to follow a CIN(-)MSI(-) pathway. ..
  35. Chen W, Chen J, Liu J, Lin W, King K, Whang Peng J, et al. Microsatellite instability in sporadic-colon-cancer patients with and without liver metastases. Int J Cancer. 1997;74:470-4 pubmed
    ..Our data suggest that tumor progression may involve increased genetic instability. ..
  36. Teyssier J, Rousset F, Garcia E, Cornillet P, Laubriet A. Upregulation of the netrin receptor (DCC) gene during activation of b lymphocytes and modulation by interleukins. Biochem Biophys Res Commun. 2001;283:1031-6 pubmed
    ..In contrast no effect has been detected after activation of T cells by anti-CD3. These data suggest that the DCC encoded netrin receptor is involved in B cell immunopoiesis. ..
  37. Baldus S. [Clinical, pathological and molecular prognostic factors in colorectal carcinomas]. Pathologe. 2003;24:49-60 pubmed
    ..In the future, so-called response predictors will presumably gain a certain relevance in the context of neoadjuvant (radiotherapy) chemotherapy. The present review summarizes these results and discusses the future clinical relevance. ..
  38. Starostik P, Greiner A, Schultz A, Zettl A, Peters K, Rosenwald A, et al. Genetic aberrations common in gastric high-grade large B-cell lymphoma. Blood. 2000;95:1180-7 pubmed
    ..Several known TSGs, namely, the APC, p15/p16, p53, and DCC genes, were found to suffer frequent LOH during lymphomagenesis...
  39. Hedrick L, Cho K, Fearon E, Wu T, Kinzler K, Vogelstein B. The DCC gene product in cellular differentiation and colorectal tumorigenesis. Genes Dev. 1994;8:1174-83 pubmed
    ..These results provide evidence that DCC encodes a cell surface-localized protein and emphasize the inverse relationship between differentiation and tumorigenesis. ..
  40. Fearon E. DCC: is there a connection between tumorigenesis and cell guidance molecules?. Biochim Biophys Acta. 1996;1288:M17-23 pubmed
    ..Though many additional studies are needed to characterize DCC function more definitively, it seems reasonable to predict that such studies are likely to provide new insights into growth control pathways in normal and cancer tissues. ..
  41. Furne C, Rama N, Corset V, Chedotal A, Mehlen P. Netrin-1 is a survival factor during commissural neuron navigation. Proc Natl Acad Sci U S A. 2008;105:14465-70 pubmed publisher
    ..Thus, adequate commissural neurons navigation requires both the attractive activity of netrin-1 and the anti-apoptotic function of this cue. ..
  42. Horstmann M, Pösl M, Scholz R, Anderegg B, Simon P, Baumgaertl K, et al. Frequent reduction or loss of DCC gene expression in human osteosarcoma. Br J Cancer. 1997;75:1309-17 pubmed
    ..In view of the putative tumour-suppressor characteristics of the DCC gene its loss or reduction of expression could be a specific event in the development or progression of many high-grade osteosarcomas. ..
  43. Deiner M, Sretavan D. Altered midline axon pathways and ectopic neurons in the developing hypothalamus of netrin-1- and DCC-deficient mice. J Neurosci. 1999;19:9900-12 pubmed
    ..Netrin protein localization also indicates that unlike in more caudal CNS, guidance about the hypothalamic ventral midline does not require midline expression of netrin. ..
  44. Wettergren Y, Odin E, Nilsson S, Willen R, Carlsson G, Gustavsson B. Low expression of reduced folate carrier-1 and folylpolyglutamate synthase correlates with lack of a deleted in colorectal carcinoma mRNA splice variant in normal-appearing mucosa of colorectal carcinoma patients. Cancer Detect Prev. 2005;29:348-55 pubmed
    ..The results may provide a basis for a detailed investigation of molecular mechanisms involved in folate regulation of DCC expression. ..
  45. Gervaz P, Bucher P, Morel P. Two colons-two cancers: paradigm shift and clinical implications. J Surg Oncol. 2004;88:261-6 pubmed
    ..In the future, clinical decision-making regarding adjuvant chemotherapy might be stratified according to the MSI status of cancers located proximally to the splenic flexure. ..
  46. Grann A, Zauber P. Is there a predictive value for molecular markers in predicting response to radiation and chemotherapy in rectal cancer?. Int J Radiat Oncol Biol Phys. 2002;54:1286-7 pubmed
  47. Bamias A, Yu Z, Weinberger P, Markakis S, Kowalski D, Camp R, et al. Automated quantitative analysis of DCC tumor suppressor protein in ovarian cancer tissue microarray shows association with beta-catenin levels and outcome in patients with epithelial ovarian cancer. Ann Oncol. 2006;17:1797-802 pubmed
    ..003). Low nuclear DCC levels predict for poor patient outcome in epithelial ovarian cancer. DCC may exert its antitumor function, in part, through regulation of beta-catenin levels. ..
  48. Mehlen P, Goldschneider D. [Dependence receptors DCC and UNC5H: the role of apoptosis in the control of tumorigenesis]. J Soc Biol. 2005;199:211-8 pubmed
    ..In this review, we will describe the implication of the netrin-1/receptor pairs as novel negative regulators of tumor development. ..
  49. de Jong M, Te Meerman G, van der Graaf W, de Vries E, Nolte I, Mulder M, et al. No association between the Arg201Gly polymorphism of the DCC gene and colorectal cancer. Dig Liver Dis. 2004;36:821-3 pubmed
    ..No association was observed between the Arg201Gly polymorphism of DCC and colorectal cancer risk. ..
  50. Meyerhardt J, Look A, Bigner S, Fearon E. Identification and characterization of neogenin, a DCC-related gene. Oncogene. 1997;14:1129-36 pubmed
    ..However, the chromosomal location and ubiquitous expression of NGN in various human tumors suggest it is infrequently altered in cancer. ..
  51. Cong W, Finkelstein S, Wu M. [Relationship between genetic alterations and clinicopathological features in intrahepatic cholangiocarcinoma]. Zhonghua Bing Li Xue Za Zhi. 2001;30:183-7 pubmed
    ..The detection of the pedigree of genetic alterations in ICC may provide useful information for evaluating the state of tumor progression and clinic prognosis. ..
  52. Zhao Y, Piao C, Hei T. Tumor suppressor function of Betaig-h3 gene in radiation carcinogenesis. Adv Space Res. 2003;31:1575-82 pubmed
    ..The findings provide strong evidence that the Betaig-h3 gene has tumor suppressor function in radiation-induced tumorigenic human bronchial epithelial cells and suggest a potential target for interventional therapy. ..
  53. Li P, Liu M, Ni J. [Study on the expression of the gene deleted in colorectal carcinoma in ovarian carcinoma]. Zhonghua Fu Chan Ke Za Zhi. 2003;38:207-9 pubmed
    ..The results indicated that loss of DCC gene expression may play an important role in ovarian carcinomas and its progression. ..