Abstract
To elucidate further the genetic mechanisms for follicular thyroid tumor development and progression, we allelotyped follicular thyroid tumors and other thyroid lesions from 92 patients. In general, a low frequency of loss of heterozygosity (LOH) was found, the highest being for chromosomes 3q, 10q, 11p, 11q, 13q, and 22q (10%–15%). However, detailed study of LOH of these chromosome arms with regard to the different histopathological diagnoses indicates that a locus on chromosome 10q may be involved in follicular thyroid tumor progression. In addition, the majority of Hürthle cell adenomas showed LOH on either chromosome 3q or 18q, in contrast to the other tumor types. This discrepancy in genetic alterations may contribute to the divergent clinical features occurring in these tumors.
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Antonini P. Vénuat AM, Linares G, Caillou B, Schlumberger M, Travagli JP, Berger R, Parmentier C (1991) Cytogenetic abnormalities in thyroid adenomas. Cancer Genet Cytogenet 52:157–164
Antonini P, Lévy N, Caillou B, Vénuat A-M, Schlumberger M, Parmentier C, Bernheim A (1993) Numerical aberrations, including trisomy 22 as the sole anomaly, are recurrent in follicular thyroid adenomas. Genes Chromosom Cancer 8:63–66
Bartnitzke S, Hermann ME, Lobeck H, Zuschneid W, Neuhaus P, Bullerdiek J (1989) Cytogenetic findings on eight follicular adenomas including one with a t(10;19). Cancer Genet Cytogenet 39:65–68
Belge G, Thode B, Bullerdiek J, Bartnitzke S (1991) Deletion of part of the long arm of chromosome 13 as the only karyotypic aberration in a follicular thyroid adenoma. Cancer Genet Cytogenet 56:277–280
Belge G, Thode B, Bullerdiek J, Bartnitzke S (1992) Aberrations of chromosome 19. Do they characterize a subtype of benign thyroid adenomas? Cancer Genet Cytogenet 60:23–26
Beige G, Thode B, Rippe V, Bartnitzke S, Bullerdiek J (1994) A characteristic sequence of trisomies starting with trisomy 7 in benign thyroid tumors. Hum Genet 94:198–202
Bergerheim U, Nordenskjöld M, Collins VP (1989) Deletion mapping in renal cell carcinoma. Cancer Res 49:1390–1396
Cryns VL, Thor A, Hong-Ji X, Shi-Xue H, Wierman ME, Vickery AL, Benedict WF, Arnold A (1994) Loss of the retinoblastoma tumor-suppressor gene in parathyroid carcinoma. N Engl J Med 330:757–761
Donghi R, Longoni A, Pilotti S, Michieli P, Della Porta G, Pierotti MA (1993) Gene p53 mutations are restricted to poorly differentiated and undifferentiated carcinomas of the thyroid gland. J Clin Invest 91:1753–1760
Fagin JA (1992) Molecular defects in thyroid gland neoplasia. J Clin Endocrinol Metab 75:1398–1400
Fagin JA, Matsuo K, Karmakar A, Chen DL, Tang S-H, Koeffler HP (1993) High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest 91:179–184
Farid NR, Shi Y, Zou M (1994) Molecular basis of thyroid cancer. Endocrine Rev 15:202–232
Goretzki PE, Lyons J, Stacy-Phipps S, Rosenau W, Demeure M, Clark OH, McCormick F, Röher H-D, Bourne HR (1992) Mutational activation of RAS and GSP oncogenes in differentiated thyroid cancer and their biological implications. World J Surg 16:576–582
Hedinger CE, Williams ED, Sobin LH (1988) Histological typing of thyroid tumours. The WHOs international histological classification of tumours, 2nd rev edn. Springer, Berlin Heidelberg New York
Herrmann MA, Hay ID, Bartelt DH, Ritland SR, Dahl RJ, Grant CS, Jenkins RB (1991) Cytogenetic and molecular genetic studies of follicular and papillary thyroid cancers. J Clin Invest 88:1596–1604
Hicks DG, LiVolsi VA, Neidich JA, Puck JM, Kant JA (1990) Clonal analysis of solitary follicular nodules in the thyroid. Am J Pathol 137:553–562
Ito T, Seyama T, Mizuno T, Tsuyama N, Hayashi T, Hayashi Y, Dohi K, Nakamura N, Akiyama M (1992) Unique association of p53 mutations with undifferentiated but not with differentiated carcinomas of the thyroid gland. Cancer Res 52:1369–1371
Jenkins RB, Hay ID, Herath JF, Schultz CG, Spurbeck JL, Grant CS, Goellner JR, Dewald GW (1990) Frequent occurrence of cytogenetic abnormalities in sporadic nonmedullary thyroid carcinoma. Cancer 66:1213–1220
Kubo K, Yoshimoto K, Yokogoshi Y, Tsuyuguchi M, Saito S (1991) Loss of heterozygosity on chromosome 1p in thyroid adenoma and medullary carcinoma, but not in papillary carcinoma. Jpn J Cancer Res 82:1097–1103
Larsson C, Byström C, Skoog L, Rotstein S, Nordenskjöld M (1990) Genomic alterations in human breast carcinomas. Genes Chromosom Cancer 2:191–197
Lemoine NR, Mayall ES, Wyllie FS, Williams ED, Goyns M, Stringer B, Wynford-Thomas D (1989) High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis. Oncogene 4:159–164
Matsuo K, Tang S-H, Fagin JA (1991) Allelotype of human thyroid tumors: loss of chromosome 11q13 sequences in follicular neoplasms. Mol Endocrinol 5:1873–1879
Namba H, Rubin SA, Fagin JA (1990a) Point mutations of ras oncogenes are an early event in thyroid tumorigenesis. Mol Endocrinol 4:1474–1479
Namba H, Matsuo K, Fagin JA (1990b) Clonal composition of benign and malignant human thyroid tumors. J Clin Invest 86:120–125
O'Sullivan C, Barton CM, Staddon SL, Brown CL, Lemoine NR (1991) Activating point mutations of the gsp oncogene in human thyroid adenomas. Mol Carcinog 4:345–349
Parma J, Duprez L, Sande J van, Cochaux P, Gervy C, Mockel J, Dumont J, Vassart G (1993) Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature 365:649–651
Roque L, Castedo S, Clode A, Soares J (1992) Translocation t(5; 19): a recurrent change in thyroid follicular adenoma. Genes Chromosom Cancer 4:346–347
Roque L, Castedo S. Clode A, Soares J (1993) Deletion of 3p25 →pter in a primary follicular thyroid carcinoma and its metastasis. Genes Chromosom Cancer 8:199–203
Sparkes RS, Ling SM, Muller H (1978) Ring 10 chromosome: 46, XX, r10(p15q26). Hum Genet 43:341–345
Suarez HG, Villard JA du, Severino M, Caillou B, Schlumberger M, Tubiana M, Parmentier C, Monier R (1990) Presence of mutations in all three ras genes in human thyroid tumors. Oncogene 5:565–570
Suarez HG, Villard JA du, Caillou B, Schlumberger M, Parmentier C, Monier R (1991) gsp mutations in human thyroid tumours. Oncogene 6:677–679
Taruscio D, Carcangiu ML, Ried T, Ward DC (1994) Numerical chromosomal aberrations in thyroid tumors detected by double fluorescence in situ hybridization. Genes Chromosom Cancer 9:180–185
Tommerup N, Lothe R (1992) Constitutional ring chromosomes and tumour suppressor genes. J Med Genet 29:879–882
Wynford-Thomas D (1993) Molecular basis of epithelial tumorigenesis: the thyroid model. Crit Rev Oncog 4:1–23
Zedenius J, Auer G, Bäckdahl M, Falkmer U, Grimelius L, Lundell G, Wallin G (1992) Follicular tumors of the thyroid gland; diagnosis, clinical aspects and nuclear DNA content. World J Surg 16:589–594
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Zedenius, J., Wallin, G., Svensson, A. et al. Allelotyping of follicular thyroid tumors. Hum Genet 96, 27–32 (1995). https://doi.org/10.1007/BF00214182
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DOI: https://doi.org/10.1007/BF00214182