Molecular genetics of thyroid tumors and surgical decision-making

World Journal of Surgery

Volumn 24, Issue 8, 2000, Pages 923-933

  Learoyd, Diana L ^a,b   Messina, Marinella ^a,b   Zedenius, Jan ^c   Robinson, Bruce G ^a,b  

^a ROYAL NORTH SHORE HOSPITAL   (Australia)

^b UNIVERSITY OF SYDNEY   (Australia)

^c KAROLINSKA INSTITUTE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; HETEROZYGOSITY LOSS; HUMAN; LIGAND BINDING; MEDICAL DECISION MAKING; MOLECULAR GENETICS; ONCOGENE; ONCOGENE RAS; PATHOGENESIS; PATIENT CARE; PHENOTYPE; SEQUENCE ANALYSIS; THYROID TUMOR; TUMOR SUPPRESSOR GENE;

DECISION MAKING; DNA, NEOPLASM; GENES, TUMOR SUPPRESSOR; GENETIC SCREENING; HUMANS; MOLECULAR BIOLOGY; PROTO-ONCOGENES; THYROID NEOPLASMS;

EID: 0033911338     PISSN: 03642313     EISSN: None     Source Type: Journal    
DOI: 10.1007/s002680010164     Document Type: Article

References (124)

1. Fagin, J.A.: Genetic basis of endocrine disease. 3. Molecular defects in thyroid gland neoplasia. J. Clin. Endocrinol. Metab. 75:1398, 1992
2. Farid, N.R., Shi, Y., Zou, M.: Molecular basis of thyroid cancer. Endocr. Rev. 15:202, 1994
3. Trupp, M., Arenas, E., Fainzilber, M., Nilsson, A-S., Sieber, B-A., Grigoriou, M., Kilkenny, C., Salazar-Grueso, E., Pachnis, V., Arumae, U., Sariola, H., Saarma, M., Ibanez, C.F.: Functional receptor for GDNF encoded by the c-ret proto-oncogene. Nature 381:785, 1996
4. Klein, R.D., Sherman, D., Ho, W.H., Stone, D., Bennett, G.L., Moffat, B., Vandlen, R., Simmons, L., Gu, Q.M., Hongo, J.A., Devaux, B., Poulsen, K., Armanini, M., Nozaki, C., Asai, N., Goddard, A., Phillips, H., Henderson, C.E., Takahashi, M., Rosenthal, A.: A gpi-linked protein that interacts with ret to form a candidate neurturin receptor. Nature 392:210, 1998
5. Milbrandt, J., Desauvage, F.J., Fahrner, T.J., Baloh, R.H., Leitner, M.L., Tansey, M.G., Lampe, P.A., Heuckeroth, R.O., Kotzbauer, P.T., Simburger, K.S., Golden, J.P., Davies, J.A., Vejsada, R., Kato, A.C., Hynes, M., Sherman, D., Nishimura, M., Wang, L.C., Vandlen, R., Moffat, B., Klein, R.D., Poulsen, K., Gray, C., Garces, A., Henderson, C.E.: Persephin, a novel neurotrophic factor related to gdnf and neurturin. Neuron 20:245, 1998
6. Schuchardt, A., D'Agati, V., Larsson-Blomberg, L., Costantini, F., Pachnis, V.: Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367:380, 1994
7. Fusco, A., Grieco, M., Santoro, M., Berlingieri, M.T., Pilotti, S., Pierotti, M.A., Della Porta, G., Vecchio, G.: A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases. Nature 328:170, 1987
8. Grieco, M., Santoro, M., Berlingieri, M.T., Melillo, R.M., Donghi, R., Bongarzone, I., Pierotti, M.A., Della Porta, G., Fusco, A., Vecchio, G.: 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, 1990
9. Pierotti, M.A., Santoro, M., Jenkins, R.B., Sozzi, G., Bongarzone, I., Grieco, M., Monzini, N., Miozzo, M., Herrmann, M.A., Fusco, A., Hay, I.D., Della Porta, G., Vecchio, G.: 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, 1992
10. Santoro, M., Dathan, N.A., Berlingieri, M.T., Bongarzone, I., Paulin, C., Grieco, M., Pierotti, M.A., Vecchio, G., Fusco, A.: Molecular characterization of RET/PTC3; a novel rearranged version of the RETproto-oncogene in a human thyroid papillary carcinoma. Oncogene 9:509, 1994
11. Jhiang, S.M., Smanik, P.A., Mazzaferri, E.L.: Development of a single-step duplex RT-PCR detecting different forms of ret activation, and identification of the third form of in vivo ret activation in human papillary thyroid carcinoma. Cancer Lett. 78:69, 1994
12. Bongarzone, I., Monzini, N., Borrello, M.G., Carcano, C., Ferraresi, G., Arighi, E., Mondellini, P., Della Porta, G., Pierotti, M.A.: Molecular characterization of a thyroid tumor-specific transforming sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RIa of cyclic AMP-dependent protein kinase A. Mol. Cell. Biol. 13:358, 1993
13. Sozzi, G., Bongarzone, I., Miozzo, M., Borrello, M.G., Blutti, M.G., Pilotti, S., Della Porta, G., Pierotti, M.A.: A t(10;17) translocation creates the RET/PTC2 chimcric transforming sequence in papillary thyroid carcinoma. Genes Chromosomes Cancer 9:244, 1994
14. Klugbauer, S., Lengfelder, E., Demidchik, E.P., Rabes, H.M.: A new form of RET rearrangement in thyroid carcinomas of children after the Chernobyl reactor accident. Oncogene 13:1099, 1996
15. Fugazzola, L., Pierotti, M.A., Vigano, E., Pacini, F., Vorontsova, T.V., Bongarzone, I.: Molecular and biochemical analysis of RET/ PTC4, a novel oncogenic rearrangement between RET and ELE1 genes, in a post-Chernobyl papillary thyroid cancer. Oncogene 13: 1093, 1996
16. Klugbauer, S., Demidchik, E.P., Lengfelder, E., Rabes, H.M.: Detection of a novel type of RET rearrangement (PTC5) in thyroid carcinomas after Chernobyl and analysis of the involved RET-fused gene RFG5. Cancer Res. 58:198, 1998
17. Viglietto, G., Chiappetta, G., Martinez Tello, F.J., Fukunaga, F.H., Tallini, G., Rigopoulou, D., Visconti, R., Mastro, A., Santoro, M., Fusco, A.: RET/PTC oncogene activation is an early event in thyroid carcinogenesis. Oncogene 11:1207, 1995
18. Zou, M., Shi, Y., Farid, N.R.: Low rate of ret proto-oncogene activation (PTC/retTPC) in papillary thyroid carcinomas from Saudi Arabia. Cancer 73:176, 1994
19. Sugg, S.L., Zheng, L., Rosen, I.E., Freeman, J.L., Ezzat, S., Asa, S.L.: ret/PTC-1, -2, and -3 oncogene rearrangements in human thyroid carcinomas: implications for metastatic potential? J. Clin. Endocrinol. Metab. 81:3360, 1996
20. Bounacer, A., Wicker, R., Caillou, B., Cailleux, A.F., Sarasin, A., Schlumberger, M., Suarez, H.G.: High prevalence of activating ret proto-oncogene rearrangements, in thyroid tumors from patients who had received external radiation. Oncogene 15:1263, 1997
21. Nikiforov, Y.E., Rowland, J.M., Bove, K.E., Monforte Munoz, H., Fagin, J.A.: Distinct pattern of ret oncogene rearrangements in morphological variants of radiation-induced and sporadic thyroid papillary carcinomas in children. Cancer Res. 57:1690, 1997
22. Mayr, B., Goretzki, P., Ruschoff, J., Dralle, H.: Ret/PTC-1, -2, and -3 oncogene rearrangements in human thyroid carcinomas: implications for metastatic potential [letter]? J. Clin. Endocrinol. Metab. 82:1306, 1997
23. Tallini, G., Santoro, M., Helie, M., Carlomagno, F., Salvatore, G., Chiappetta, G., Carcangiu, M.L., Fusco, A.: Ret/ptc oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes. Clin. Cancer Res. 4:287, 1998
24. Soares, P., Fonseca, E., Wynfordthomas, D., Sobrinhosimoes, M.: Sporadic ret-rearranged papillary carcinoma of the thyroid: a subset of slow growing, less aggressive thyroid neoplasms. J. Pathol. 185:71, 1998
25. Bongarzone, I., Vigneri, P., Mariani, L., Collini, P., Pilotti, S., Pierotti, M.A.: Ret/ntrk1 rearrangements in thyroid gland tumors of the papillary carcinoma family: correlation with clinicopathological features. Clin. Cancer Res. 4:223, 1998
26. Learoyd, D.L., Messina, M., Zedenius, J., Guinea, A.I., Delbridge, L., Robinson, B.G.: RET/PTC and RET tyrosine kinase expression in adult papillary thyroid carcinomas. J. Clin. Endocrinol. Metab. 83:3631, 1998
27. Ron, E., Lubin, J.H., Shore, R.E., Mabuchi, K., Modan, B., Pottern, L.M., Schneider, A.B., Tucker, M.A., Boice, J.D.: Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Radiat. Res. 141:259, 1995
28. Fagin, J.A.: Familial nonmedullary thyroid carcinoma: the case for genetic susceptibility [editorial]. J. Clin. Endocrinol. Metab. 82:342, 1997
29. Ito, T., Seyama, T., Iwamoto, K.S., Mizuno, T., Tronko, N.D., Komissarenko, I.V., Cherstovoy, E.D., Satow, Y., Takeichi, N., Dohi, K., Akiyama, M.: Activated RET oncogene in thyroid cancers of children from areas contaminated by Chernobyl accident. Lancet 344: 259, 1994
30. Fugazzola, L., Pilotti, S., Pinchera, A., Vorontsova, T.V., Mondellini, P., Bongarzone, I., Greco, A., Astakhova, L., Butti, M.G., Demidchik, E.P., Pacini, F., Pierotti, M.A.: Oncogenic rearrangements of the RET proto-oncogenc in papillary thyroid carcinomas from children exposed to the Chernobyl nuclear accident. Cancer Res. 55: 5617, 1995
31. Klugbauer, S., Lengfelder, E., Demidchik, E.P., Rabes, H.M.: High prevalence of RET rearrangement in thyroid tumors of children from Belarus after the Chernobyl reactor accident. Oncogene 11: 2459, 1995
32. Pacini, F., Vorontsova, T., Demidchik, E., Molinaro, E., Agate, L., Romei, C., Shavrova, E., Cherstvoy, E.D., Ivashkevitch, Y., Kuchinskaya, E., Schlumberger, M., Ronga, G., Filesi, M., Pinchear, A.: Post-Chernobyl thyroid carcinoma in Belarus children and adolescents: comparison with naturally occurring thyroid carcinoma in Italy and France. J. Clin. Endocrinol. Metab. 82:3563, 1997
33. Robbins, J., Schneider, A.B.: Radioiodine-induccd thyroid cancer: studies in the aftermath of the accident at Chernobyl. Trends Endocrinol. Metab. 9:87, 1998
34. Ito, T., Seyama, T., Iwamoto, K.S., Hayashi, T., Mizuno, T., Tsuyama, N., Dohi, K., Nakamura, N., Akiyama, M.: In vitro irradiation is able to cause RET oncogene rearrangement. Cancer Res. 53:2940, 1993
35. Mizuno, T., Kyoizumi, S., Suzuki, T., Iwamoto, K.S., Seyama, T.: Continued expression of a tissue specific activated oncogene in the early steps of radiation-induced human thyroid carcinogcnesis. Oncogene 15:1455, 1997
36. Fogelfeld, L., Bauer, T.K., Schneider, A.B., Swartz, J.E., Zitman, R.: p53 Gene mutations in radiation-induced thyroid cancer. J. Clin. Endocrinol. Metab. 81:3039, 1996
37. Challeton, C., Bounacer, A., Du Villard, J.A., Caillou, B., De Vathaire, F., Monier, R., Schlumberger, M., Saurez, H.G.: Pattern of ras and gsp oncogene mutations in radiation-associated human thyroid tumors. Oncogene 11:601, 1995
38. Nikiforov, Y.E., Nikiforova, M.N., Gnepp, D.R., Fagin, J.A.: Prevalence of mutations of ras and p53 in benign and malignant thyroid tumors from children exposed to radiation after the Chernobyl nuclear accident. Oncogene 13:687, 1996
39. Suchy, B., Waldmann, V., Klugbauer, S., Rabes, H.M.: Absence of ras and p53 mutations in thyroid carcinomas of children after Chernobyl in contrast to adult thyroid tumours. Br. J. Cancer 77:952, 1998
40. O'Riordain, D.S., O'Brien, T., Crotty, T.B., Gharib, H., Grant, C.S., van Heerden, J.A.: Multiple endocrine neoplasia type 2B: more than an endocrine disorder. Surgery 118:936, 1995
41. Mulligan, L.M., Kwok, J.B.J., Healey, C.S., Elsdon, M.J., Eng, C., Gardner, E., Love, D.R., Mole, S.E., Moore, J.K., Papl, L., Ponder, M.A., Telenius, H., Tunnacliffe, A., Ponder, B.A.J.: Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 363:458, 1993
42. Donis Keller, H., Dou, S., Chi, D., Carlson, K.M., Toshima, K., Lairmore, T.C., Howe, J.R., Molcy, J.F., Goodfellow, P., Wells, S.A., Jr.: Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum. Mol. Genet. 2:851, 1993
43. Eng, C., Clayton, D., Schuffenecker, I., Lenoir, G.M., Cote, G.J., Gagel, R.F., Ploos van Amstel, H-K., Lips, C.J.M., Nishisho, I., Takai, S-I., Marsh, D.J., Robinson, B.G., Frank-Raue, K., Raue, F., Xue, F., Noll, W.W., Romei, C., Pacini, F., Fink, M., Niederle, B., Zedenius, J. Nordenskjold, M., Komminoth, P., Hendy, G.N., Gharib, H., Thibodeau, S.N., Lacroix, A., Frilling, A., Ponder, B.A.J., Mulligan, L.M.: The relationship between specific RET proto-oncogene mutations and disease phenotypc in multiple endocrine neoplasia type 2: international RET mutation consortium analysis. J.A.M.A. 276:1575, 1996
44. Santoro, M., Carlomagno, F., Romano, A., Boltaro, D.P., Dathan, N.A., Grieco, M., Fusco, A., Vecchio, G., Matoskova, B., Kraus, M.H., Di Fiore, P.P.: Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B. Science 267: 381, 1995
45. Asai, N., Iwashita, T., Matsuyama, M., Takahashi, M.: Mechanism of activation of the ret proto-oncogene by multiple endocrine neoplasia 2A mutations. Mol. Cell. Biol. 15:1613, 1995
46. Songyang, Z., Carraway, K.L., Eck, M.J., Harrison, S.C., Feldman, R.A., Mohammadi, M., Schlessinger, J., Hubbard, S.R., Smith, D.P., Eng, C. Lorenzo, M.J., Ponder, B.A.J., Mayer, B.J., Cantley, L.C.: Catalytic specificity of protein tyrosine kinases is critical for selective signalling. Nature 373:536, 1995
47. Berndt, I., Reuter, M., Sailer, B., Frankraue, K., Groth, P., Grussendorf, M., Raue, F., Ritter, M.M., Hoppner, W.: A new hot spot for mutations in the ret protooncogene causing familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2a. J. Clin. Endocrinol. Metab. 83:770, 1998
48. Schuffenecker, I., Virallymonod, M., Brohet, R., Goldgar, D., Contedevolx, C., Lcclerc, L., Chabre, O., Boneu, A., Caron, J., Houdent, C., Modigliani, E., Rohmer, V., Schlumberger, M., Eng, C., Guillausseau, P.J., Lenoir, G.M.: Risk and penetrance of primary hyperparathyroidism in multiple endocrine neoplasia type 2a families with mutations at codon 634 of the ret proto-oncogene. J. Clin. Endocrinol. Metab. 83:487, 1998
49. Marsh, D.J., McDowall, D., Hyland, V.J., Andrew, S.D., Schnitzler, M., Gaskin, E.L., Nevell, D.F., Diamond, T., Delbridge, L., Clifton Bligh, P., Robinson, E.G.: The identification of false positive responses to the pentagastrin stimulation test in RET mutation negative members of MEN 2A families. Clin. Endocrinol. (Oxf.) 44:213, 1996
50. Guyetant S, Rousselet, M.C., Durigon, M., Chappard, D., Franc, B., Guerin, O., Saint-Andre, J.P.: Sex-related C cell hyperplasia in the normal human thyroid: a quantitative autopsy study. J. Clin. Endocrinol. Metab. 82:42, 1997
51. Lallier, M., Stvil, D., Giroux, M., Huot, C., Gaboury, L., Oligny, L., Desjardins, J.G.: Prophylactic thyroidectomy for medullary thyroid carcinoma in gene carriers of MEN2 syndrome. J. Pediatr. Surg. 33:846, 1998
52. Dralle, H., Gimm, O., Simon, D., Frankraue, K., Gortz, G., Niederle, B., Wahl, R.A., Koch, B., Walgenbach, S., Hampel, R., Ritter, M.M, Spelsberg, F., Heiss, A., Hinze, R., Hoppner, W.: Prophylactic thyroidectomy in 75 children and adolescents with hereditary medullary thyroid carcinoma: German and Austrian experience. World J. Surg. 22:744, 1998
53. Wells, S.A., Skinner, M.A.: Prophylactic thyroidectomy, based on direct genetic testing, in patients at risk for the multiple endocrine neoplasia type 2 syndromes. Exp. Clin. Endocrinol. Diabetes 106:29, 1998
54. Learoyd, D.L., Marsh, D.J., Richardson, A-L., Twigg, S.M., Delbridge, L., Robinson, B.G.: Genetic testing for familial cancer: consequences of RET proto-oncogene mutation analysis in multiple endocrine neoplasia type 2. Arch. Surg. 132:1022, 1997
55. Learoyd, D.L., Capes, A.G., Robinson, B.G.: Multiple endocrine neoplasia type 2 and glial cell line-derived neurotrophic factor. Curr. Opin. Endocrinol. Diabetes 4:130, 1997
56. Zedenius, J., Larsson, C., Bergholm, U., Bovee, J., Svensson, A., Hallengren, B., Grimelius, L., Backdahl, M., Weber, G., Wallin, G.: Mutations of codon 918 in the RET proto-oncogene correlate to poor prognosis in sporadic medullary thyroid carcinomas. J. Clin. Endocrinol. Metab. 80:3088, 1995
57. Marsh, D.J., Learoyd, D.L., Andrew, S.D., Krishnan, L., Pojer, R., Richardson, A-L., Delbridge, L., Eng, C., Robinson, B.G.: Somatic mutations in the RET proto-oncogene in sporadic medullary thyroid carcinoma. Clin. Endocrinol. (Oxf.) 44:249, 1996
58. Marsh, D.J., Andrew, S.D., Eng, C., Learoyd, D.L., Capes, A.G., Pojer, R., Richardson, A.L., Houghton, C., Mulligan, L.M., Ponder, B.A., Robinson, B.G.: Germline and somatic mutations in an oncogene: RET mutations in inherited medullary thyroid carcinoma. Cancer Res. 56:1241, 1996
59. Pasini, A., Geneste, O., Legrand, P., Schlumberger, M., Rossel, M., Fournier, L., Rudkin, B.B., Schuffenecker, I., Lenoir, G.M., Billaud, M.: Oncogenic activation of RET by two distinct FMTC mutations affecting the tyrosine kinase domain. Oncogene 15:393, 1997
60. Eng, C., Mulligan, L.M., Healey, C.S., Houghton, C., Frilling, A., Raue, F., Thomas, G.A., Ponder, B.A.: Heterogeneous mutation of the RET proto-oncogene in subpopulations of medullary thyroid carcinoma. Cancer Res 56:2167, 1996
61. Wohllk, N., Cote, G.J., Bugalho, M.M.J., Ordonez, N., Evans, D.B., Goepfert, H., Khorana, S., Schultz, P., Richards, C.S., Gagel, R.F.: Relevance of ret proto-oncogene mutations in sporadic medullary thyroid carcinoma. J. Clin. Endocrinol. Metab. 81-3740, 1996
62. Loh, K-C.: Familial nonmedullary thyroid carcinoma: a meta-review of case series. Thyroid 7:107, 1997
63. Burgess, J.R., Duffield, A., Wilkinson, S.J., Ware, R., Greenaway, T.M., Percival, J., Hoffman, L.: Two families with an autosomal dominant inheritance pattern for papillary carcinoma of the thyroid. J. Clin. Endocrinol. Metab. 82:345, 1997
64. Lupoli, G., Vitale, G., Caraglia, M., Fittipaldi, M.R., Abbruzzese, A., Tagliaferri, P., Bianoc, A.R.: Familial papillary thyroid microcarcinoma: a new clinical entity. Lancet 353:637, 1999
65. McKay, J.D., Williamson, J., Lesueur, F., Stark, M., Duffield, A., Canzian, F., Romeo, G., Hoffman, L.: At least three genes account for familial papillary thyroid carcinoma: TCO and MNG1 excluded as susceptibility loci from a large Tasmanian family. Eur. J. Endocrinol. 141:122, 1999
66. Bignell, G.R., Canzian, F., Shayeghi, M., Stark, M.. Shugart, Y.Y., Biggs, P., Mangion, J., Hamoudi, R., Rosenblatt, J., Buu, P., Sun, S., Stoffer, S.S., Goldgar, D.E., Romeo, G., Houlston, R.S., Narod, S.A., Stratton, M.R., Foulkes, W.D.: Familial nontoxic multinodular thyroid goiter locus maps to chromosome 14q but docs not account for familial nonmedullary thyroid cancer. Am. J. Hum. Genet. 61:1123, 1997
67. Canzian, F., Amati, P., Harach, H.R., Kraimps, J.L., Lesueur, F., Barbier, J., Levillain, P., Romeo, G., Bonneau, D.: A gene predisposing to familial thyroid tumors with cell oxyphilia maps to chromosome 19p13.2. Am. J. Hum. Genet. 63:1743, 1998
68. Pierotti, M.A., Bongarzone, I., Borrello, M.G., Greco, A., Pilotti, S., Sozzi, G.: Cytogenetics and molecular genetics of carcinomas arising from thyroid epithelial follicular cells. Genes Chromosomes Cancer 16:1, 1996
69. Di Renzo, M.F., Olivero, M., Ferro, S., Prat, M., Bongarzone, I., Pilotti, S., Belfiore, A., Costantino, A., Vigneri, R., Pierotti, M.A.: Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas. Oncogene 7:2549, 1992
70. Parma, J., Duprez, L., Van Sande, J., Cochaux, P., Gervy, C., Mockel, J., Dumont, J., Vassart, G.: Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature 365:649, 1993
71. Russo, D., Arturi, F., Schlumberger, M., Caillou, B., Monier, R., Filetti, S., Suarez, H.G.: Activating mutations of the TSH receptor in differentiated thyroid carcinomas. Oncogene 11:1907, 1995
72. Russo, D., Arturi, F., Wicker, R., Chazenbalk, G.D., Schlumberger, M., Du Villard, J.A., Caillou, B., Monier, R., Rapoport, B., Filetti, S., Suarez, H.G.: Genetic alterations in thyroid hyperfunctioning adenomas. J. Clin. Endocrinol. Metab. 80:1347, 1995
73. Russo, D., Arturi, F., Suarez, H.G., Schlumberger, M., Du Villard, J.A., Crocetti, U., Filetti, S.: Thyrotropin receptor gene alterations in thyroid hyperfunctioning adenomas. J. Clin. Endocrinol. Metab. 81: 1548, 1996
74. 2+ cascades. Mol. Endocrinol. 9:725, 1995
75. Fuhrer, D., Holzapfel, H.P., Wonerow, P., Scherbaum, W.A., Paschke, R.: Somatic mutations in the thyrotropin receptor gene and not in the Gs alpha protein gene in 31 toxic thyroid nodules. J. Clin. Endocrinol. Metab. 82:3885, 1997
76. Duprez, L., Parma, J., Costagliola, S., Hermans, J., Van-Sande, J, Dumont, J.E., Vassart, G.: Constitutive activation of the TSH receptor by spontaneous mutations affecting the N-terminal extracellular domain. F.E.B.S. Lett. 409:469, 1997
77. Parma, J., Duprez, L., Van-Sande, J., Hermans, J., Rocmans, P., Van-Vliet, G., Costagliola, S., Rodien, P., Dumont, J.E., Vassart, G.; Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas. J. Clin. Endocrinol. Metab. 82:2695, 1997
78. Tonacchera, M., Chiovato, L., Pinchera, A., Agretti, P., Fiore, E., Cetani, F., Rocchi, R., Viacava, P., Miccoli, P., Vitti, P.: Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma. J. Clin. Endocrinol. Metab. 83:492, 1998
79. Spambalg, D., Sharifi, N., Elisei, R., Gross, J.L., Medeiros Neto, G., Fagin, J.A.: Structural studies of the thyrotropin receptor and Gs alpha in human thyroid cancers: low prevalence of mutations predicts infrequent involvement in malignant transformation. J. Clin. Endocrinol. Metab. 81:3898, 1996
80. Lyons, J., Landis, C.A., Harsh, G., Vallar, L., Grunewald, K., Feichtinger, H., Duh, Q.Y., Clark, O.H., Kawasaki, E., Bourne, H.R., McCormick, F.: Two G protein oncogenes in human endocrine tumors. Science 249:655, 1990
81. Weinstein, L.S., Shenker, A., Gejman, P.V., Merino, M.J., Friedman, E., Spiegel, A.M.: Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N. Engl. J. Med. 325:1688, 1991
82. Suarez, H.G.: Genetic alterations in human epithelial thyroid tumours. Clin. Endocrinol. (Oxf.) 48:531, 1998
83. Goretzki, P.E., Lyons, J., Stacy Phipps, S., Rosenau, W., Demeure, M., Clark, O.H., McCormick, F., Roher, H.D., Bourne, H.R.: Mutational activation of RAS and GSP oncogenes in differentiated thyroid cancer and their biological implications. World J. Surg. 16: 576, 1992
84. Namba, H., Gutman, R.A., Matsuo, K., Alvarez, A., Fagin, J.A.: H-ras protooncogene mutations in human thyroid neoplasms. J. Clin. Endocrinol. Metab. 71:223, 1990
85. McCormick, F.: Activators and effectors of ras p21 proteins. Curr. Opin. Genet. Dev. 4:71, 1994
86. Ezzat, S., Zheng, L., Kolenda, J., Safarian, A., Freeman, J.L., Asa, S.L.: Prevalence of activating ras mutations in morphologically characterised thyroid nodules. Thyroid 6:409, 1996
87. Lemoine, N.R., Mayall, E.S., Wyllie, F.S., Farr, C.J., Hughes, D., Padua, R.A., Thurston, V., Williams, E.D., Wynford Thomas, D.: Activated ras oncogenes in human thyroid cancers. Cancer Res. 48:4459, 1988
88. Said, S., Schlumberger, M., Suarez, H.G.: Oncogenes and anti-oncogenes in human epithelial thyroid tumors. J. Endocrinol. Invest. 17:371, 1994
89. Karga, H., Lee, J.K., Vickery, A.L., Jr., Thor, A., Gaz, R.D., Jameson, J.L.: Ras oncogene mutations in benign and malignant thyroid neoplasms. J. Clin. Endocrinol. Metab. 73:832, 1991
90. Hara, H., Fulton, N., Yashiro, T., Ito, K., DeGroot, L.J., Kaplan, E.L.: N-ras mutation: an independent prognostic factor for aggressiveness of papillary thyroid carcinoma. Surgery 116:1010, 1994
91. Zedenius, J., Larsson, C., Wallin, G., Backdahl, M., Aspenblad, U., Hoog, A., Borresen, A.L., Auer, G.: Alterations of p53 and expression of WAF1/p21 in human thyroid tumors. Thyroid 6:1, 1996
92. Kamb, A., Gruis, N.A., Weaver Feldhaus, J., Liu, Q., Harshman, K., Tavtigian, S.V., Stockert, E., Day, R.S., Johnson, B.E., Skolnick, M.H.: A cell regulator potentially involved in genesis of many tumor types. Science 264:436, 1994
93. Greenblatt, M.S., Bennett, W.P., Hollstein, M., Harris, C.C.: Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 54:4855, 1994
94. Zou, M., Shi, Y., Farid, N.R.: p53 mutations in all stages of thyroid carcinomas. J. Clin. Endocrinol. Metab. 77:1054, 1993
95. Fagin, F.A., Matsuo, K., Karmakar, A., Chen, D.L., Tang, S.H., Koeffler, H.P.: High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J. Clin. Invest. 91: 179, 1993
96. Ito, T., Seyama, T., Mizuno, T., Tsuyama, N., Hayashi, T., Hayashi, Y., Dohi, K., Nakamura, N., Akiyama, M.: Unique association of p53 mutations with undifferentiated but not with differentiated carcinomas of the thyroid gland. Cancer Res. 52:1369, 1992
97. Donghi, R., Longoni, A., Pilotti, S., Michieli, P., Della, P.G., Pierotti, M.A.: Gene p53 mutations are restricted to poorly differentiated and undifferentiated carcinoma of the thyroid gland. J. Clin. Invest. 91:1753, 1993
98. Jossart, G.H., Epstein, H.D., Shaver, J.K., Weier, H.U., Greulich, K.M., Tezelman, S., Grossman, R.F., Siperstein, A.E., Duh, Q.Y., Clark, O.H.: Immunocytochemical detection of p53 in human thyroid carcinomas is associated with mutation and immortalization of cell lines. J. Clin. Endocrinol. Metab. 81:3498, 1996
99. Pacini, F., Pinchera, A., Mancusi, F., Pollina, L., Fontanini, G., Bevilacqua, G., Miccoli, P., Basolo, F.: Anaplastic thyroid carcinoma: a retrospective clinical and immunohistochemical study. Oncol. Rep. 1:921, 1994
100. Shi, Y., Zou, M., Farid, N.R., al-Sedairy, S.T.: Evidence of gene deletion of p21 (WAF1/CIP1), a cyclin-dependent protein kinase inhibitor, in thyroid carcinomas. Br. J. Cancer 74:1336, 1996
101. Goretzki, P.E., Gorelov, V., Dotzenrath, C., Witte, J., Roeher, H.D.: A frequent mutation/polymorphism in tumor suppressor gene INK4B (MTS-2) in papillary and medullary thyroid cancer. Surgery 120:1081, 1996
102. Jones, C.J., Shaw, J.J., Wyllie, F.S., Gaillard, N., Schlumberger, M., Wynfordthomas, D.: High frequency deletion of the tumour suppressor gene p16(Ink4a) (Mts1) in human thyroid cancer cell lines. Mol. Cell. Endocrinol. 116:115, 1996
103. Harach, H.R., Williams, G.T., Williams, E.D.: Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm. Histopathology 25:549, 1994
104. Zeki, K., Spambalg, D., Sharifi, N., Gonsky, R., Fagin, J.A.: Mutations of the adenomatous polyposis coli gene in sporadic thyroid neoplasms. J. Clin. Endocrinol. Metab. 79:1317, 1994
105. Colletta, G., Sciacchitano, S., Palmirotta, R., Ranieri, A., Zanella, E., Cama, A., Costantini, R.M., Battista, P., Pontecorvi, A.: Analysis of adenomatous polyposis coli gene in thyroid tumours. Br. J. Cancer 70:1085, 1994
106. Cetta, F., Chiappetta, G., Melillo, R.M., Petracci, M., Montalto, G., Santoro, M., Fusco, A.: The ret/ptc1 oncogene is activated in familial adenomatous polyposis-associated thyroid papillary carcinomas. J. Clin. Endocrinol. Metab. 83:1003, 1998
107. Liaw, D., Marsh, D.J., Li, J., Dahia, P.L., Wang, S.I., Zheng, Z., Bose, S., Call, K.M., Tsou, H.C., Peacocke, M., Eng, C., Parsons, R.: Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat. Genet. 16:64, 1997
108. Eng, C.: Genetics of Cowden-syndrome: through the looking glass of oncology. Int. J. Oncol. 12:701, 1998
109. Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S.I., Pue, J., Miliaresis, C., Rodgers, L., Mccombie, R., Bigner, S.H., Giovanella, B.C., Ittmann, M. Tycko, B., Hibshoosh, H., Wigler, M.H. Parsons, R.: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275: 1943, 1997
110. Steck, P.A., Pershouse, M.A., Jasser, S.A., Yung, W.K.A., Lin, H., Ligon, A.H., Langford, L.A., Baumgard, M.L., Hattier, T., Davis, T., Frye, C., Hu, R., Swedlund, B., Teng, D.H.F., Tavtigian, S.V.: Identification of a candidate tumour suppressor gene, mmacl, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat. Genet. 15:356, 1997
111. Zedenius, J., Wallin, G., Svensson, A., Bovee, J., Hoog, A., Backdahl, M., Larsson, C.: Deletions of the long arm of chromosome 10 in progression of follicular thyroid tumors. Hum. Genet. 97:299, 1996
112. Zedenius, J., Wallin, G., Svensson, A., Grimelius, L., Hoog, A., Lundell, G., Backdahl, M., Larsson, C.: Allelotyping of follicular thyroid tumors. Hum. Genet. 96:27, 1995
113. Marsh, D.J., Zhcng, Z., Zedenius, J., Kremer, H., Padberg, G.W., Larsson, C., Longy, M., Eng, C.: Differential loss of heterozygosity in the region of the Cowden locus within 10q22-23 in follicular thyroid adenomas and carcinomas. Cancer Res. 57:500, 1997
114. Dahia, P.L., Marsh, D.J., Zheng, Z., Zedenius, J., Komminoth, P., Frisk, T., Wallin, G., Parsons, R., Longy, M., Larsson, C., Eng, C.: Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors. Cancer Res. 57:4710, 1997
115. Yeh, J.J., Marsh, D.J., Zedenius, J., Dwight, T., Delbridge, L., Robinson, B.G., Eng, C.: Fine-structure deletion mapping of 10q22-24 identifies regions of loss of heterozygosity and suggests that sporadic follicular thyroid adenomas and follicular thyroid carcinoma develop along distinct neoplastic pathways. Genes Chromosomes Cancer 26:322, 1999
116. Herrmann, M.A., Hay, I.D., Bartelt, D.H., Jr., Ritland, S.R., Dahl, R.J., Grant, C.S., Jenkins, R.B.: Cytogenetic and molecular genetic studies of follicular and papillary thyroid cancers. J. Clin. Invest. 88:1596, 1991
117. Grebe, S.K., McIver, B., Hay, I.D., Wu, P.S., Maciel, L.M., Drabkin, H.A., Goellner, J.R., Grant, C.S., Jenkins, R.B., Eberhardt, N.L.: Frequent loss of heterozyosity on chromosomes 3p and 17p without VHL or p53 mutations suggests involvement of unidentified tumor suppressor genes in follicular thyroid carcinoma. J. Clin. Endocrinol. Metab. 82:3684, 1997
118. Ward, L.S., Brenta, G., Medvedovic, M., Fagin, J.A.: Studies of allelic loss in thyroid tumors reveal major differences in chromosomal instability between papillary and follicular carcinomas. J. Clin. Endocrinol. Metab. 83:525, 1998
119. Trovato, M., Fragetta, F., Villari, D., Batolo, D., Mackey, K., Trimarchi, F., Benvenga, S.: Loss of heterozygosity of the long arm of chromosome 7 in follicular and anaplastic thyroid cancer, but not in papillary thyroid cancer. J. Clin. Endocrinol. Metab. 84:3235, 1999
120. Brabant, G., Hoang Vu, C., Cetin, Y., Dralle, H., Scheumann, G., Moine, J., Hansson, G., Jansson, S., Ericson, L.E., Nilsson, M.: E-cadherin: a differentiation marker in thyroid malignancies. Cancer Res. 53:4987, 1993
121. Hotz, H.G., Runkel, N.S.F., Frankraue, K., Raue, F., Buhr, H.J.: Prophylactic thyroidectomy in MEN IIa: does the calcitonin level correlate with tumor spread. Langenbecks Arch. Surg. 383:170, 1998
122. Zedenius, J., Dwight, T., Robinson, B.G., Delbridge, L., Backdahl, M., Wallin, G., Larsson, C., Weber, G.: A rapid method for DNA extraction from fine needle biopsies of thyroid tumors, and subsequent RET mutation analysis. Cancer Detect. Prev. 22:544, 1998
123. Romei, C., Elisei, R., Pinchera, A., Ceccherini, I., Molinaro, E., Mancusi, F., Martino, E., Romeo, G., Pacini, F.: Somatic mutations of the ret protooncogene in sporadic medullary thyroid carcinoma are not restricted to exon 16 and are associated with tumor recurrence. J. Clin. Endocrinol. Metab. 81:1619, 1996
124. Scurini, C., Quadro, L., Fattoruso, O., Verga, U., Libroia, A., Lupoli, G., Cascone, E., Marzano, L., Paracchi, S., Busnardo, B., Girelli, M.E., Bellstella, A., Colantuoni, V.: Germline and somatic mutations of the ret proto-oncogene in apparently sporadic medullary thyroid carcinomas. Mol. Cell. Endocrinol. 137:51, 1998