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Gene Review

CCDC6  -  coiled-coil domain containing 6

Homo sapiens

Synonyms: Coiled-coil domain-containing protein 6, D10S170, H4, PTC, Papillary thyroid carcinoma-encoded protein, ...
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Disease relevance of CCDC6


Psychiatry related information on CCDC6

  • We investigated the accuracy of intraoperative tumour classification in papillary thyroid cancers (PTC) and its effect on intraoperative decision-making [6].

High impact information on CCDC6

  • We designated this transforming gene PTC (for papillary thyroid carcinoma) [1].
  • We have determined the nucleotide sequence of a continuous 2100 bp segment of DNA including both H3 and H4 coding sequences, the entire spacer DNA separating the genes and surrounding nonhistone DNA [7].
  • We have cloned and characterized members of a small multigene family that encodes late-stage histone H3 and H4 mRNAs from the sea urchin Lytechinus pictus [7].
  • Unlike their highly repetitive histone gene counterparts, which are expressed at an earlier developmental stage, late H3 and H4 histone genes are not present in tandem repeats [7].
  • We have isolated five clones containing human histone genes from a human genomic DNA library, using a cloned X. laevis histone H4 cDNA probe (pX1ch4) [8].

Chemical compound and disease context of CCDC6


Biological context of CCDC6


Anatomical context of CCDC6


Associations of CCDC6 with chemical compounds

  • In most cases the activation consisted of the fusion of its tyrosine-kinase domain with the 5'-terminal region of a gene designated H4 or D10S170 [22].
  • Refined localization to contiguous regions on chromosome 10q of the two genes (H4 and RET) that form the oncogenic sequence PTC [23].
  • Mutational analysis showed that the amino-terminal H4 leucine zipper domain (amino acids 55-93), as well as H4 amino acids 101 to 386, was required for efficient induction of factor-independent growth of Ba/F3 cells [4].
  • ZD6474 prevented the growth of two human PTC cell lines that carry spontaneous RET/PTC1 rearrangements [9].
  • Activating mutations in RAS genes were detected in 15% of FA, 33% of FTC and 7% of PTC [24].

Regulatory relationships of CCDC6

  • Ninety per cent of ret/PTC-1-positive tumours failed to express H4, a phenomenon that has not been described previously and which may have considerable bearing on tumour morphology [25].

Other interactions of CCDC6


Analytical, diagnostic and therapeutic context of CCDC6


  1. PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas. Grieco, M., Santoro, M., Berlingieri, M.T., Melillo, R.M., Donghi, R., Bongarzone, I., Pierotti, M.A., Della Porta, G., Fusco, A., Vecchio, G. Cell (1990) [Pubmed]
  2. RET mutations in human disease. Pasini, B., Ceccherini, I., Romeo, G. Trends Genet. (1996) [Pubmed]
  3. Identification of a novel subtype of H4-RET rearrangement in a thyroid papillary carcinoma and lymph node metastasis. Giannini, R., Salvatore, G., Monaco, C., Sferratore, F., Pollina, L., Pacini, F., Basolo, F., Fusco, A., Santoro, M. Int. J. Oncol. (2000) [Pubmed]
  4. H4(D10S170), a gene frequently rearranged in papillary thyroid carcinoma, is fused to the platelet-derived growth factor receptor beta gene in atypical chronic myeloid leukemia with t(5;10)(q33;q22). Schwaller, J., Anastasiadou, E., Cain, D., Kutok, J., Wojiski, S., Williams, I.R., LaStarza, R., Crescenzi, B., Sternberg, D.W., Andreasson, P., Schiavo, R., Siena, S., Mecucci, C., Gilliland, D.G. Blood (2001) [Pubmed]
  5. Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors. Dahia, P.L., Marsh, D.J., Zheng, Z., Zedenius, J., Komminoth, P., Frisk, T., Wallin, G., Parsons, R., Longy, M., Larsson, C., Eng, C. Cancer Res. (1997) [Pubmed]
  6. Intraoperative tumour classification in papillary thyroid cancer--a diagnostic dilemma. Hoelting, T., Buhr, H.J., Herfarth, C. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. (1995) [Pubmed]
  7. Sea urchin (lytechinus pictus) late-stage histone H3 and H4 genes: characterization and mapping of a clustered but nontandemly linked multigene family. Childs, G., Nocente-McGrath, C., Lieber, T., Holt, C., Knowles, J.A. Cell (1982) [Pubmed]
  8. The structure of the human histone genes: clustered but not tandemly repeated. Heintz, N., Zernik, M., Roeder, R.G. Cell (1981) [Pubmed]
  9. ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases. Carlomagno, F., Vitagliano, D., Guida, T., Ciardiello, F., Tortora, G., Vecchio, G., Ryan, A.J., Fontanini, G., Fusco, A., Santoro, M. Cancer Res. (2002) [Pubmed]
  10. Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness. Guarino, V., Faviana, P., Salvatore, G., Castellone, M.D., Cirafici, A.M., De Falco, V., Celetti, A., Giannini, R., Basolo, F., Melillo, R.M., Santoro, M. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  11. Genotyping of an Italian papillary thyroid carcinoma cohort revealed high prevalence of BRAF mutations, absence of RAS mutations and allowed the detection of a new mutation of BRAF oncoprotein (BRAF(V599lns)). Carta, C., Moretti, S., Passeri, L., Barbi, F., Avenia, N., Cavaliere, A., Monacelli, M., Macchiarulo, A., Santeusanio, F., Tartaglia, M., Puxeddu, E. Clin. Endocrinol. (Oxf) (2006) [Pubmed]
  12. Localization of tryptase to human cutaneous mast cells and keratinocytes by immunofluorescence and immunoperoxidase cytochemistry with monoclonal antitryptase antibody. Schwartz, L.B., Foley, J.V., Austen, K.F., Soter, N.A., Shepard, R., Murphy, G.F. J. Allergy Clin. Immunol. (1985) [Pubmed]
  13. Fusion of H4/D10S170 to PDGFRbeta in a patient with chronic myelomonocytic leukemia and long-term responsiveness to imatinib. Drechsler, M., Hildebrandt, B., Kündgen, A., Germing, U., Royer-Pokora, B. Ann. Hematol. (2007) [Pubmed]
  14. Characterization of an inversion on the long arm of chromosome 10 juxtaposing D10S170 and RET and creating the oncogenic sequence RET/PTC. Pierotti, M.A., Santoro, M., Jenkins, R.B., Sozzi, G., Bongarzone, I., Grieco, M., Monzini, N., Miozzo, M., Herrmann, M.A., Fusco, A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  15. The oncogenic activity of RET point mutants for follicular thyroid cells may account for the occurrence of papillary thyroid carcinoma in patients affected by familial medullary thyroid carcinoma. Melillo, R.M., Cirafici, A.M., De Falco, V., Bellantoni, M., Chiappetta, G., Fusco, A., Carlomagno, F., Picascia, A., Tramontano, D., Tallini, G., Santoro, M. Am. J. Pathol. (2004) [Pubmed]
  16. Characterization of the promoter region and oligomerization domain of H4 (D10S170), a gene frequently rearranged with the ret proto-oncogene. Tong, Q., Li, Y., Smanik, P.A., Fithian, L.J., Xing, S., Mazzaferri, E.L., Jhiang, S.M. Oncogene (1995) [Pubmed]
  17. Characterization of novel non-clonal intrachromosomal rearrangements between the H4 and PTEN genes (H4/PTEN) in human thyroid cell lines and papillary thyroid cancer specimens. Puxeddu, E., Zhao, G., Stringer, J.R., Medvedovic, M., Moretti, S., Fagin, J.A. Mutat. Res. (2005) [Pubmed]
  18. A novel multicolor hybridization scheme applied to localization of a transcribed sequence (D10S170/H4) and deletion mapping in the thyroid cancer cell line TPC-1. Jossart, G.H., O'Brien, B., Cheng, J.F., Tong, Q., Jhiang, S.M., Duh, Q., Clark, O.H., Weier, H.U. Cytogenet. Cell Genet. (1996) [Pubmed]
  19. Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells. Nikiforova, M.N., Stringer, J.R., Blough, R., Medvedovic, M., Fagin, J.A., Nikiforov, Y.E. Science (2000) [Pubmed]
  20. Papillary thyroid carcinoma oncogene (RET/PTC) alters the nuclear envelope and chromatin structure. Fischer, A.H., Bond, J.A., Taysavang, P., Battles, O.E., Wynford-Thomas, D. Am. J. Pathol. (1998) [Pubmed]
  21. The oncogene associated with human papillary thyroid carcinoma (PTC) is assigned to chromosome 10 q11-q12 in the same region as multiple endocrine neoplasia type 2A (MEN2A). Donghi, R., Sozzi, G., Pierotti, M.A., Biunno, I., Miozzo, M., Fusco, A., Grieco, M., Santoro, M., Vecchio, G., Spurr, N.K. Oncogene (1989) [Pubmed]
  22. Molecular characterization of RET/PTC3; a novel rearranged version of the RETproto-oncogene in a human thyroid papillary carcinoma. Santoro, M., Dathan, N.A., Berlingieri, M.T., Bongarzone, I., Paulin, C., Grieco, M., Pierotti, M.A., Vecchio, G., Fusco, A. Oncogene (1994) [Pubmed]
  23. Refined localization to contiguous regions on chromosome 10q of the two genes (H4 and RET) that form the oncogenic sequence PTC. Sozzi, G., Pierotti, M.A., Miozzo, M., Donghi, R., Radice, P., De Benedetti, V., Grieco, M., Santoro, M., Fusco, A., Vecchio, G. Oncogene (1991) [Pubmed]
  24. BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Soares, P., Trovisco, V., Rocha, A.S., Lima, J., Castro, P., Preto, A., Máximo, V., Botelho, T., Seruca, R., Sobrinho-Simões, M. Oncogene (2003) [Pubmed]
  25. Assessment of ret/PTC-1 rearrangements in neoplastic thyroid tissue using TaqMan RT-PCR. Sheils, O.M., O'Leary, J.J., Sweeney, E.C. J. Pathol. (2000) [Pubmed]
  26. New breakpoints in both the H4 and RET genes create a variant of PTC-1 in a post-Chernobyl papillary thyroid carcinoma. Elisei, R., Romei, C., Soldatenko, P.P., Cosci, B., Vorontsova, T., Vivaldi, A., Basolo, F., Cherstvoy, E.D., Pinchera, A., Pacini, F. Clin. Endocrinol. (Oxf) (2000) [Pubmed]
  27. High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines. Xu, X., Quiros, R.M., Gattuso, P., Ain, K.B., Prinz, R.A. Cancer Res. (2003) [Pubmed]
  28. C-cell and thyroid epithelial tumours and altered follicular development in transgenic mice expressing the long isoform of MEN 2A RET. Reynolds, L., Jones, K., Winton, D.J., Cranston, A., Houghton, C., Howard, L., Ponder, B.A., Smith, D.P. Oncogene (2001) [Pubmed]
  29. Regulation of protein kinase B tyrosine phosphorylation by thyroid-specific oncogenic RET/PTC kinases. Jung, H.S., Kim, D.W., Jo, Y.S., Chung, H.K., Song, J.H., Park, J.S., Park, K.C., Park, S.H., Hwang, J.H., Jo, K.W., Shong, M. Mol. Endocrinol. (2005) [Pubmed]
  30. Detection of RET oncogene activation in human papillary thyroid carcinomas by in situ hybridisation. Fabien, N., Paulin, C., Santoro, M., Berger, N., Grieco, M., Galvain, D., Barbier, Y., Dubois, P.M., Fusco, A. Br. J. Cancer (1992) [Pubmed]
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