Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer

Journal of Clinical Investigation

Volumn 115, Issue 1, 2005, Pages 94-101

  Ciampi, Raffaele ^a   Knauf, Jeffrey A ^b   Kerler, Roswitha ^c   Gandhi, Manoj ^a   Zhu, Zhaowen ^a   Nikiforova, Marina N ^a   Rabes, Hartmut M ^c   Fagin, James A ^b   Nikiforov, Yuri E ^a,b  

^a Dept of Pathol and Lab Medicine ^*  (Germany)

^b UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^c UNIVERSITY OF MUNICH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

HYBRID PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; MUTAGENIC AGENT; NERVE GROWTH FACTOR; PROTEIN KINASE; PROTEIN RET; PROTEIN TYROSINE KINASE; AKAP9 PROTEIN, HUMAN; B RAF KINASE; BRAF PROTEIN, HUMAN; CYTOSKELETON PROTEIN; MESSENGER RNA; SIGNAL TRANSDUCING ADAPTOR PROTEIN; VALINE;

AKAP9 GENE; AMINO TERMINAL SEQUENCE; ANIMAL CELL; ARTICLE; BRAF GENE; CELL STRAIN 3T3; CELL TRANSFORMATION; CHROMOSOME 7Q; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME ACTIVITY; EXON; FUSION GENE; GENE; GENE REARRANGEMENT; GENETIC RECOMBINATION; HUMAN; HUMAN TISSUE; NONHUMAN; NTRK1 GENE; NUCLEOTIDE SEQUENCE; ONCOGENE; PARACENTRIC CHROMOSOME INVERSION; POINT MUTATION; PRIORITY JOURNAL; PROTEIN DOMAIN; RADIATION CARCINOGENESIS; SIGNAL TRANSDUCTION; THYROID CANCER; THYROID PAPILLARY CARCINOMA; ADOLESCENT; ADULT; ANIMAL; CELL LINE; CERCOPITHECUS; CHEMISTRY; CHERNOBYL ACCIDENT; CHILD; CHROMOSOME 7; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MOUSE; PAPILLARY CARCINOMA; PATHOLOGY; THYROID TUMOR; TIME; TUMOR CELL LINE;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ADOLESCENT; ADULT; ANIMALS; BASE SEQUENCE; CARCINOMA, PAPILLARY; CELL LINE, TRANSFORMED; CELL LINE, TUMOR; CERCOPITHECUS AETHIOPS; CHERNOBYL NUCLEAR ACCIDENT; CHILD; CHROMOSOMES, HUMAN, PAIR 7; CYTOSKELETAL PROTEINS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MAP KINASE SIGNALING SYSTEM; MICE; POINT MUTATION; PROTO-ONCOGENE PROTEINS B-RAF; RECOMBINANT FUSION PROTEINS; RECOMBINATION, GENETIC; RNA, MESSENGER; THYROID NEOPLASMS; TIME FACTORS; VALINE;

EID: 85047691154     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI23237     Document Type: Article

References (51)

1. Kimura, E.T., et al. 2003. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res. 63:1454-1457.
2. Soares, P., et al. 2003. BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene. 22:4578-4580.
3. Frattini, M., et al. 2004. Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer. Oncogene. 23:7436-7440.
4. Takahashi, M., Ritz, J., and Cooper, G.M. 1985. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell. 42:581-588.
5. Takahashi, M. 1988. Structure and expression of the ret transforming gene. IARC Sci. Publ. 1988:189-197.
6. Fusco, A., et al. 1987. A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases. Nature. 328:170-172.
7. Grieco, M., et al. 1990. PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas. Cell. 60:557-563.
8. Pierotti, M.A., et al. 1992. Characterization of an inversion on the long arm of chromosome 10 juxtaposing D10S170 and RET and creating the oncogenic sequence RET/PTC. Proc. Natl. Acad. Sci. U. S. A. 89:1616-1620.
9. Minoletti, F., et al. 1994. The two genes generating RET/PTC3 are localized in chromosomal band 10q11.2. Genes Chromosomes Cancer. 11:51-57.
10. Asai, N., Murakami, H., Iwashita, T., and Takahashi, M. 1996. A mutation at tyrosine 1062 in MEN2A-Ret and MEN2B-Ret impairs their transforming activity and association with she adaptor proteins. J. Biol. Chem. 271:17644-17649.
11. Knauf, J.A., Kuroda, H., Basu, S., and Fagin, J.A. 2003. RET/PTC-induced dedifferentiation of thyroid cells is mediated through Y1062 signaling through SHC-RAS-MAP kinase. Oncogene. 22:4406-4412.
12. Zhu, Z., Gandhi, M., Nikiforova, M.N., Fischer, A.M., and Nikiforov, Y.E. 2003. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Am. J. Clin. Pathol. 120:71-77.
13. Cohen, Y., et al. 2003. BRAF mutation in papillary thyroid carcinoma. J. Natl. Cancer Inst. 95:625-627.
14. Davies, H., et al. 2002. Mutations of the BRAF gene in human cancer. Nature. 417:949-954.
15. Wan, P.T., et al. 2004. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell. 116:855-867.
16. Ikawa, S., et al. 1988. B-raf, a new member of the raf family, is activated by DNA rearrangement. Mol. Cell. Biol. 8:2651-2654.
17. Miki, T., et al. 1991. Development of a highly efficient expression cDNA cloning system: application to oncogene isolation. Proc. Natl. Acad. Sci. U. S. A. 88:5167-5171.
18. Eychene, A., Barnier, J.V., Apiou, F., Dutrillaux, B., and Calothy, G. 1992. Chromosomal assignment of two human B-raf(Rmi1) proto-oncogene loci: B-raf-1 encoding the p94Braf/Rmi1 and B-raf-2, a processed pseudogene. Oncogene. 7:1657-1660.
19. Witczak, O., et al. 1999. Cloning and characterization of a cDNA encoding an A-kinase anchoring protein located in the centrosome, AKAP450. EMBO J. 18:1858-1868.
20. Takahashi, M., et al. 1999. Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus. J. Biol. Chem. 274:17267-17274.
21. Schmidt, P.H., et al. 1999. AKAP350, a multiply spliced protein kinase Á-anchoring protein associated with centrosomes. J. Biol. Chem. 274:3055-3066.
22. Gillingham, A.K., and Munro, S. 2000. The PACT domain, a conserved centrosomal targeting motif in the coiled-coil proteins AKAP450 and pericentrin. EMBO Rep. 1:524-529.
23. Takahashi, M., Yamagiwa, A., Nishimura, T., Mukai, H., and Ono, Y. 2002. Centrosomal proteins CG-NAP and kendrin provide microtubule nucleation sites by anchoring gamma-tubulin ring complex. Mol. Biol. Cell. 13:3235-3245.
24. Sithanandam, G., Kolch, W., Duh, P.M., and Rapp, U.R. 1990. Complete coding sequence of a human B-raf cDNA and detection of B-raf protein kinase with isozyme specific antibodies. Oncogene. 5:1775-1780.
25. Avruch, J., et al. 2001. Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade. Recent Prog. Horm. Res. 56:127-155.
26. Brose, M.S., et al. 2002. BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res. 62:6997-7000.
27. Rajagopalan, H., et al. 2002. Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature. 418:934.
28. Xu, X., Quiros, R.M., Gattuso, P., Ain, K.B., and Prinz, R.A. 2003. High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines. Cancer Res. 63:4561-4567.
29. Edwards, A.S., and Scott, J.D. 2000. A-kinase anchoring proteins: protein kinase A and beyond. Curr. Opin. Cell Biol. 12:217-221.
30. Takahashi, M., Mukai, H., Oishi, K., Isagawa, T., and Ono, Y. 2000. Association of immature hypophosphorylated protein kinase cepsilon with an anchoring protein CG-NAP. J. Biol. Chem. 275:34592-34596.
31. Fugazzola, L., et al. 1995. Oncogenic rearrangements of the RET proto-oncogene in papillary thyroid carcinomas from children exposed to the Chernobyl nuclear accident. Cancer Res. 55:5617-5620.
32. Klugbauer, S., Lengfelder, E., Demidchik, E.P., and Rabes, H.M. 1995. High prevalence of RET rearrangement in thyroid tumors of children from Belarus after the Chernobyl reactor accident. Oncogene. 11:2459-2467.
33. Nikiforov, Y.E., Rowland, J.M., Bove, K.E., Monforte-Munoz, H., and Fagin,J.A. 1997. Distinct pattern of ret oncogene rearrangements in morphological variants of radiation-induced and sporadic thyroid papillary carcinomas in children. Cancer Res. 57:1690-1694.
34. Smida, J., et al. 1999. Distinct frequency of ret rearrangements in papillary thyroid carcinomas of children and adults from Belarus. Int. J. Cancer. 80:32-38.
35. Rabes, H.M., et al. 2000. Pattern of radiation-induced RET and NTRK1 rearrangements in 191 post-Chernobyl papillary thyroid carcinomas: biological, phenotypic, and clinical implications. Clin. Cancer Res. 6:1093-1103.
36. Bounacer, A., et al. 1997. High prevalence of activating ret proto-oncogene rearrangements, in thyroid tumors from patients who had received external radiation. Oncogene. 15:1263-1273.
37. Collins, B.J., et al. 2002. RET expression in papillary thyroid cancer from patients irradiated in childhood for benign conditions. J. Clin. Endocrinol. Metab. 87:3941-3946.
38. Nikiforova, M.N., et al. 2004. Low prevalence of BRAF mutations in radiation-induced thyroid tumors in contrast to sporadic papillary carcinomas. Cancer Lett. 209:1-6.
39. Pierotti, M.A., et al. 1992. Characterization of an inversion on the long arm of chromosome 10 juxtaposing D10S170 and RET and creating the oncogenic sequence RET/PTC. Proc. Natl. Acad. Sci. U. S. A. 89:1616-1620.
40. Minoletti, F., et al. 1994. The two genes generating RET/PTC3 are localized in chromosomal band 10q11.2. Genes Chromosomes Cancer. 11:51-57.
41. Greco, A., et al. 1997. Chromosome 1 rearrangements involving the genes TPR and NTRK1 produce structurally different thyroid-specific TRK oncogenes. Genes Chromosomes Cancer. 19:112-123.
42. Beimfohr, C., Klugbauer, S., Demidchik, E.P., Lengfelder, E., and Rabes, H.M. 1999. NTRK1 re-arrangement in papillary thyroid carcinomas of children after the Chernobyl reactor accident. Int. J. Cancer. 80:842-847.
43. Sachs, R.K., Chen, A.M., and Brenner, D.J. 1997. Review: proximity effects in the production of chromosome aberrations by ionizing radiation. Int. J. Radiat. Biol. 71:1-19.
44. Savage, J.R. 2000. Cancer. Proximity matters. Science. 290:62-63.
45. Sachs, R.K., Brenner, D.J., Chen, A.M., Hahnfeldt, P., and Hlatky, L.R. 1997. Intra-arm and interarm chromosome intrachanges: tools for probing the geometry and dynamics of chromatin. Radiat. Res. 148:330-340.
46. Nikiforova, M.N., et al. 2000. Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells. Science. 290:138-141.
47. Smith, L.E., Nagar, S., Kim, G.J., and Morgan, W.F. 2003. Radiation-induced genomic instability: radiation quality and dose response. Health Phys. 85:23-29.
48. Little, J.B. 2003. Genomic instability and radiation. J. Radiol. Prot. 23:173-181.
49. Kunzli, B.M., et al. 2002. Influences of the lysosomal associated membrane proteins (Lamp-1, Lamp-2) and Mac-2 binding protein (Mac-2-BP) on the prognosis of pancreatic carcinoma. Cancer. 94:228-239.
50. Kawamura, K., et al. 2004. Induction of centrosome amplification and chromosome instability in human bladder cancer cells by p53 mutation and cyclin E overexpression. Cancer Res. 64:4800-4809.
51. Nikiforova, M.N., et al. 2003. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J. Clin. Endocrinol. Metab. 88:5399-5404.