Skip to main content
Erschienen in: Der Internist 7/2018

21.06.2018 | Schilddrüsenkarzinome | Schwerpunkt: Schilddrüsenerkrankungen

Genetik von Schilddrüsenknoten und Schilddrüsenkarzinomen

verfasst von: Prof. Dr. Dr. D. Führer

Erschienen in: Die Innere Medizin | Ausgabe 7/2018

Einloggen, um Zugang zu erhalten

Zusammenfassung

Schilddrüsentumoren sind außerordentlich heterogen und weisen unterschiedliche genetische Signaturen auf. Schilddrüsenkarzinome sind monoklonal, der histologische Phänotyp wird weitgehend durch die Art der somatischen Mutationen bestimmt. Die Mutationslast ist in differenzierten Schilddrüsenkarzinomen sehr niedrig, in gering differenzierten und anaplastischen Karzinomen hingegen hoch. In der zytologischen Differenzialdiagnostik von Feinnadelpunktaten kann der Mutationsnachweis hilfreich sein, eine prognostische Bedeutung hat er meist nicht. Von großer Relevanz ist die Molekularpathologie hingegen für die Entwicklung „zielgerichteter“ Therapien bei fortgeschrittenen Schilddrüsenkarzinomen und für immunonkologische Therapiekonzepte.
Literatur
1.
Zurück zum Zitat Krohn K, Führer D, Bayer Y, Eszlinger M, Brauer V, Neumann S, Paschke R (2005) Molecular pathogenesis of euthyroid and toxic multinodular goiter. Endocr Rev 26(4):504–524CrossRefPubMed Krohn K, Führer D, Bayer Y, Eszlinger M, Brauer V, Neumann S, Paschke R (2005) Molecular pathogenesis of euthyroid and toxic multinodular goiter. Endocr Rev 26(4):504–524CrossRefPubMed
2.
Zurück zum Zitat Führer D, Bockisch A, Schmid KW (2012) Euthyroid goiter with and without nodules—diagnosis and treatment. Dtsch Arztebl Int 109(29–30):506–515PubMedPubMedCentral Führer D, Bockisch A, Schmid KW (2012) Euthyroid goiter with and without nodules—diagnosis and treatment. Dtsch Arztebl Int 109(29–30):506–515PubMedPubMedCentral
3.
Zurück zum Zitat Studer H, Derwahl M (1995) Mechanisms of nonneoplastic endocrine hyperplasia—a changing concept: a review focused on the thyroid gland. Endocr Rev 16(4):411–426PubMed Studer H, Derwahl M (1995) Mechanisms of nonneoplastic endocrine hyperplasia—a changing concept: a review focused on the thyroid gland. Endocr Rev 16(4):411–426PubMed
4.
Zurück zum Zitat Kimura T, Van Keymeulen A, Golstein J, Fusco A, Dumont JE, Roger PP (2001) Regulation of thyroid cell proliferation by TSH and other factors: a critical evaluation of in vitro models. Endocr Rev 22(5):631–656CrossRefPubMed Kimura T, Van Keymeulen A, Golstein J, Fusco A, Dumont JE, Roger PP (2001) Regulation of thyroid cell proliferation by TSH and other factors: a critical evaluation of in vitro models. Endocr Rev 22(5):631–656CrossRefPubMed
5.
Zurück zum Zitat Müller K, Führer D, Mittag J, Klöting N, Blüher M, Weiss RE, Many MC, Schmid KW, Krohn K (2011) TSH compensates thyroid-specific IGF-I receptor knockout and causes papillary thyroid hyperplasia. Mol Endocrinol 25(11):1867–1879CrossRefPubMedPubMedCentral Müller K, Führer D, Mittag J, Klöting N, Blüher M, Weiss RE, Many MC, Schmid KW, Krohn K (2011) TSH compensates thyroid-specific IGF-I receptor knockout and causes papillary thyroid hyperplasia. Mol Endocrinol 25(11):1867–1879CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Führer D, Schmid KW (2010) Benign thyroid nodule or thyroid cancer? Internist (Berl) 51(5):611–619CrossRef Führer D, Schmid KW (2010) Benign thyroid nodule or thyroid cancer? Internist (Berl) 51(5):611–619CrossRef
7.
Zurück zum Zitat Versteyhe S, Driessens N, Ghaddhab C, Tarabichi M, Hoste C, Dumont JE, Miot F, Corvilain B, Detours V (2013) Comparative analysis of the thyrocytes and T cells: responses to H2O2 and radiation reveals an H2O2-induced antioxidant transcriptional program in thyrocytes. J Clin Endocrinol Metab 98(10):E1645–E1654CrossRefPubMed Versteyhe S, Driessens N, Ghaddhab C, Tarabichi M, Hoste C, Dumont JE, Miot F, Corvilain B, Detours V (2013) Comparative analysis of the thyrocytes and T cells: responses to H2O2 and radiation reveals an H2O2-induced antioxidant transcriptional program in thyrocytes. J Clin Endocrinol Metab 98(10):E1645–E1654CrossRefPubMed
8.
Zurück zum Zitat Karger S, Weidinger C, Krause K, Sheu SY, Aigner T, Gimm O, Schmid KW, Dralle H, Fuhrer D (2009) FOXO3a: a novel player in thyroid carcinogenesis? Endocr Relat Cancer 16(1):189–199CrossRefPubMed Karger S, Weidinger C, Krause K, Sheu SY, Aigner T, Gimm O, Schmid KW, Dralle H, Fuhrer D (2009) FOXO3a: a novel player in thyroid carcinogenesis? Endocr Relat Cancer 16(1):189–199CrossRefPubMed
9.
Zurück zum Zitat Karger S, Krause K, Engelhardt C, Weidinger C, Gimm O, Dralle H, Sheu-Grabellus SY, Schmid KW, Fuhrer D (2012) Distinct pattern of oxidative DNA damage and DNA repair in follicular thyroid tumours. J Mol Endocrinol 48(3):193–202CrossRefPubMed Karger S, Krause K, Engelhardt C, Weidinger C, Gimm O, Dralle H, Sheu-Grabellus SY, Schmid KW, Fuhrer D (2012) Distinct pattern of oxidative DNA damage and DNA repair in follicular thyroid tumours. J Mol Endocrinol 48(3):193–202CrossRefPubMed
11.
Zurück zum Zitat Krohn K, Führer D, Holzapfel HP, Paschke R (1998) Clonal origin of toxic thyroid nodules with constitutively activating thyrotropin receptor mutations. J Clin Endocrinol Metab 83(1):130–134PubMed Krohn K, Führer D, Holzapfel HP, Paschke R (1998) Clonal origin of toxic thyroid nodules with constitutively activating thyrotropin receptor mutations. J Clin Endocrinol Metab 83(1):130–134PubMed
12.
Zurück zum Zitat Cheung L, Messina M, Gill A, Clarkson A, Learoyd D, Delbridge L, Wentworth J, Philips J, Clifton-Bligh R, Robinson BG (2003) Detection of the PAX8-PPAR gamma fusion oncogene in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab 88(1):354–357CrossRefPubMed Cheung L, Messina M, Gill A, Clarkson A, Learoyd D, Delbridge L, Wentworth J, Philips J, Clifton-Bligh R, Robinson BG (2003) Detection of the PAX8-PPAR gamma fusion oncogene in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab 88(1):354–357CrossRefPubMed
13.
Zurück zum Zitat Kleinau G, Neumann S, Grüters A, Krude H, Biebermann H (2013) Novel insights on thyroid-stimulating hormone receptor signal transduction. Endocr Rev 34(5):691–724CrossRefPubMedPubMedCentral Kleinau G, Neumann S, Grüters A, Krude H, Biebermann H (2013) Novel insights on thyroid-stimulating hormone receptor signal transduction. Endocr Rev 34(5):691–724CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Führer D, Holzapfel HP, Wonerow P, Scherbaum WA, Paschke R (1997) 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(11):3885–3891PubMed Führer D, Holzapfel HP, Wonerow P, Scherbaum WA, Paschke R (1997) 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(11):3885–3891PubMed
15.
Zurück zum Zitat Nikiforova MN, Lynch RA, Biddinger PW, Alexander EK, Dorn GW 2nd, Tallini G, Kroll TG, Nikiforov YE (2003) RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab 88(5):2318–2326CrossRefPubMed Nikiforova MN, Lynch RA, Biddinger PW, Alexander EK, Dorn GW 2nd, Tallini G, Kroll TG, Nikiforov YE (2003) RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab 88(5):2318–2326CrossRefPubMed
16.
Zurück zum Zitat Krause K, Prawitt S, Eszlinger M, Ihling C, Sinz A, Schierle K, Gimm O, Dralle H, Steinert F, Sheu SY, Schmid KW, Fuhrer D (2011) Dissecting molecular events in thyroid neoplasia provides evidence for distinct evolution of follicular thyroid adenoma and carcinoma. Am J Pathol 179(6):3066–3074CrossRefPubMedPubMedCentral Krause K, Prawitt S, Eszlinger M, Ihling C, Sinz A, Schierle K, Gimm O, Dralle H, Steinert F, Sheu SY, Schmid KW, Fuhrer D (2011) Dissecting molecular events in thyroid neoplasia provides evidence for distinct evolution of follicular thyroid adenoma and carcinoma. Am J Pathol 179(6):3066–3074CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Führer D, Gimm O, Brabant G, Rosenbaum-Krumme S, Schilddrüsenkarzinom SKW (2014) Rationelle Diagnostik und Therapie. In: Lehnert H (Hrsg) Endokrinologie, Diabetologie und Stoffwechsel, 3. Aufl. Thieme, Stuttgart Führer D, Gimm O, Brabant G, Rosenbaum-Krumme S, Schilddrüsenkarzinom SKW (2014) Rationelle Diagnostik und Therapie. In: Lehnert H (Hrsg) Endokrinologie, Diabetologie und Stoffwechsel, 3. Aufl. Thieme, Stuttgart
18.
Zurück zum Zitat Führer D, Musholt T, Schmid KW (2017) Molekulare Pathogenese von Schilddrüsenknoten – Bedeutung für die klinische Versorgung. Laryngorhinootologie 96(9):590–596CrossRefPubMed Führer D, Musholt T, Schmid KW (2017) Molekulare Pathogenese von Schilddrüsenknoten – Bedeutung für die klinische Versorgung. Laryngorhinootologie 96(9):590–596CrossRefPubMed
19.
Zurück zum Zitat Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA (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(7):1454–1457PubMed Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA (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(7):1454–1457PubMed
20.
Zurück zum Zitat Soares P, Trovisco V, Rocha AS, Lima J, Castro P, Preto A, Máximo V, Botelho T, Seruca R, Sobrinho-Simões M (2003) BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene 22(29):4578–4580CrossRefPubMed Soares P, Trovisco V, Rocha AS, Lima J, Castro P, Preto A, Máximo V, Botelho T, Seruca R, Sobrinho-Simões M (2003) BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene 22(29):4578–4580CrossRefPubMed
21.
Zurück zum Zitat Nikiforova MN, Stringer JR, Blough R, Medvedovic M, Fagin JA, Nikiforov YE (2000) Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells. Science 290(5489):138–141CrossRefPubMed Nikiforova MN, Stringer JR, Blough R, Medvedovic M, Fagin JA, Nikiforov YE (2000) Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells. Science 290(5489):138–141CrossRefPubMed
22.
Zurück zum Zitat Cancer Genome Atlas Research Network (2014) Integrated genomic characterization of papillary thyroid carcinoma. Cell 159(3):676–690CrossRef Cancer Genome Atlas Research Network (2014) Integrated genomic characterization of papillary thyroid carcinoma. Cell 159(3):676–690CrossRef
23.
Zurück zum Zitat Falchook GS, Millward M, Hong D, Naing A, Piha-Paul S, Waguespack SG, Cabanillas ME, Sherman SI, Ma B, Curtis M, Goodman V, Kurzrock R (2015) BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer. Thyroid 25(1):71–77CrossRefPubMedPubMedCentral Falchook GS, Millward M, Hong D, Naing A, Piha-Paul S, Waguespack SG, Cabanillas ME, Sherman SI, Ma B, Curtis M, Goodman V, Kurzrock R (2015) BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer. Thyroid 25(1):71–77CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Kim KB, Cabanillas ME, Lazar AJ, Williams MD, Sanders DL, Ilagan JL, Nolop K, Lee RJ, Sherman SI (2013) Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAF(V600E) mutation. Thyroid 23(10):1277–1283CrossRefPubMedPubMedCentral Kim KB, Cabanillas ME, Lazar AJ, Williams MD, Sanders DL, Ilagan JL, Nolop K, Lee RJ, Sherman SI (2013) Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAF(V600E) mutation. Thyroid 23(10):1277–1283CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Dummer R, Schadendorf D, Ascierto PA, Larkin J, Lebbé C, Hauschild A (2015) Integrating first-line treatment options into clinical practice: what’s new in advanced melanoma? Melanoma Res 25(6):461–469CrossRefPubMed Dummer R, Schadendorf D, Ascierto PA, Larkin J, Lebbé C, Hauschild A (2015) Integrating first-line treatment options into clinical practice: what’s new in advanced melanoma? Melanoma Res 25(6):461–469CrossRefPubMed
26.
Zurück zum Zitat Zhang Y, Yu J, Lee C, Xu B, Sartor MA, Koenig RJ (2015) Genomic binding and regulation of gene expression by the thyroid carcinoma-associated PAX8-PPARG fusion protein. Oncotarget 6(38):40418–40432PubMedPubMedCentral Zhang Y, Yu J, Lee C, Xu B, Sartor MA, Koenig RJ (2015) Genomic binding and regulation of gene expression by the thyroid carcinoma-associated PAX8-PPARG fusion protein. Oncotarget 6(38):40418–40432PubMedPubMedCentral
27.
Zurück zum Zitat Ricarte-Filho JC, Ryder M, Chitale DA, Rivera M, Heguy A, Ladanyi M, Janakiraman M, Solit D, Knauf JA, Tuttle RM, Ghossein RA, Fagin JA (2009) Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1. Cancer Res 69(11):4885–4893CrossRefPubMedPubMedCentral Ricarte-Filho JC, Ryder M, Chitale DA, Rivera M, Heguy A, Ladanyi M, Janakiraman M, Solit D, Knauf JA, Tuttle RM, Ghossein RA, Fagin JA (2009) Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1. Cancer Res 69(11):4885–4893CrossRefPubMedPubMedCentral
28.
30.
Zurück zum Zitat Liu T, Wang N, Cao J, Sofiadis A, Dinets A, Zedenius J et al (2014) The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas. Oncogene 33(42):4978–4984CrossRefPubMed Liu T, Wang N, Cao J, Sofiadis A, Dinets A, Zedenius J et al (2014) The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas. Oncogene 33(42):4978–4984CrossRefPubMed
31.
Zurück zum Zitat Shi X, Liu R, Qu S, Zhu G, Bishop J, Liu X et al (2015) Association of TERT promoter mutation 1,295,228 C〉T with BRAF V600E mutation, older patient age, and distant metastasis in anaplastic thyroid cancer. J Clin Endocrinol Metab 100(4):E632–7CrossRefPubMedPubMedCentral Shi X, Liu R, Qu S, Zhu G, Bishop J, Liu X et al (2015) Association of TERT promoter mutation 1,295,228 C〉T with BRAF V600E mutation, older patient age, and distant metastasis in anaplastic thyroid cancer. J Clin Endocrinol Metab 100(4):E632–7CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Xing M, Liu R, Liu X, Murugan AK, Zhu G, Zeiger MA et al (2014) BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol 32(25):2718–2726CrossRefPubMedPubMedCentral Xing M, Liu R, Liu X, Murugan AK, Zhu G, Zeiger MA et al (2014) BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol 32(25):2718–2726CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Melo M, da Rocha AG, Vinagre J, Batista R, Peixoto J, Tavares C, Celestino R, Almeida A, Salgado C, Eloy C, Castro P, Prazeres H, Lima J, Amaro T, Lobo C, Martins MJ, Moura M, Cavaco B, Leite V, Cameselle-Teijeiro JM, Carrilho F, Carvalheiro M, Máximo V, Sobrinho-Simões M, Soares P (2014) TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab 99(5):E754–65CrossRefPubMedPubMedCentral Melo M, da Rocha AG, Vinagre J, Batista R, Peixoto J, Tavares C, Celestino R, Almeida A, Salgado C, Eloy C, Castro P, Prazeres H, Lima J, Amaro T, Lobo C, Martins MJ, Moura M, Cavaco B, Leite V, Cameselle-Teijeiro JM, Carrilho F, Carvalheiro M, Máximo V, Sobrinho-Simões M, Soares P (2014) TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab 99(5):E754–65CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Kunstman JW, Juhlin CC, Goh G, Brown TC, Stenman A, Healy JM et al (2015) Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing. Hum Mol Genet 24(8):2318–2312CrossRefPubMedPubMedCentral Kunstman JW, Juhlin CC, Goh G, Brown TC, Stenman A, Healy JM et al (2015) Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing. Hum Mol Genet 24(8):2318–2312CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Latteyer S, Tiedje V, König K, Ting S, Heukamp LC, Meder L, Schmid KW, Führer D, Moeller LC (2016) Targeted next-generation sequencing for TP53, RAS, BRAF, ALK and NF1 mutations in anaplastic thyroid cancer. Endocrine 54(3):733–741CrossRefPubMed Latteyer S, Tiedje V, König K, Ting S, Heukamp LC, Meder L, Schmid KW, Führer D, Moeller LC (2016) Targeted next-generation sequencing for TP53, RAS, BRAF, ALK and NF1 mutations in anaplastic thyroid cancer. Endocrine 54(3):733–741CrossRefPubMed
36.
Zurück zum Zitat Tiedje V, Ting S, Herold T, Synoracki S, Latteyer S, Moeller LC, Zwanziger D, Stuschke M, Fuehrer D, Schmid KW (2017) NGS based identification of mutational hotspots for targeted therapy in anaplastic thyroid carcinoma. Oncotarget 8(26):42613–42620CrossRefPubMedPubMedCentral Tiedje V, Ting S, Herold T, Synoracki S, Latteyer S, Moeller LC, Zwanziger D, Stuschke M, Fuehrer D, Schmid KW (2017) NGS based identification of mutational hotspots for targeted therapy in anaplastic thyroid carcinoma. Oncotarget 8(26):42613–42620CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Kelly LM, Barila G, Liu P, Evdokimova VN, Trivedi S, Panebianco F, Gandhi M, Carty SE, Hodak SP, Luo J, Dacic S, Yu YP, Nikiforova MN, Ferris RL, Altschuler DL, Nikiforov YE (2014) Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer. Proc Natl Acad Sci USA 111(11):4233–4238CrossRefPubMedPubMedCentral Kelly LM, Barila G, Liu P, Evdokimova VN, Trivedi S, Panebianco F, Gandhi M, Carty SE, Hodak SP, Luo J, Dacic S, Yu YP, Nikiforova MN, Ferris RL, Altschuler DL, Nikiforov YE (2014) Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer. Proc Natl Acad Sci USA 111(11):4233–4238CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Smith N, Nucera C (2015) Personalized therapy in patients with anaplastic thyroid cancer: targeting genetic and epigenetic alterations. J Clin Endocrinol Metab 100(1):35–42CrossRefPubMed Smith N, Nucera C (2015) Personalized therapy in patients with anaplastic thyroid cancer: targeting genetic and epigenetic alterations. J Clin Endocrinol Metab 100(1):35–42CrossRefPubMed
40.
Zurück zum Zitat Tiedje V, Stuschke M, Weber F, Dralle H, Moss L, Führer D (2018) Anaplastic thyroid carcinoma: review of treatment protocols. Endocr Relat Cancer 25(3):R153–R161CrossRefPubMed Tiedje V, Stuschke M, Weber F, Dralle H, Moss L, Führer D (2018) Anaplastic thyroid carcinoma: review of treatment protocols. Endocr Relat Cancer 25(3):R153–R161CrossRefPubMed
41.
Zurück zum Zitat Tiedje V, Kroiss M, Dralle H, Ting S, Stuschke M, Flentje M, Bauer S, Weber F, Brabant G, Lorenz K, Fassnacht M, Führer D, Schmid KW (2015) Protokoll zur multimodalen Therapie des anaplastischen Schilddrüsenkarzinoms. Endokrinol Inf 39(3):66–65 Tiedje V, Kroiss M, Dralle H, Ting S, Stuschke M, Flentje M, Bauer S, Weber F, Brabant G, Lorenz K, Fassnacht M, Führer D, Schmid KW (2015) Protokoll zur multimodalen Therapie des anaplastischen Schilddrüsenkarzinoms. Endokrinol Inf 39(3):66–65
42.
Zurück zum Zitat Rosove MH, Peddi PF, Glaspy JA (2013) BRAF V600E inhibition in anaplastic thyroid cancer. N Engl J Med 368(7):684–685CrossRefPubMed Rosove MH, Peddi PF, Glaspy JA (2013) BRAF V600E inhibition in anaplastic thyroid cancer. N Engl J Med 368(7):684–685CrossRefPubMed
43.
Zurück zum Zitat Wagle N, Grabiner BC, Van Allen EM, Amin-Mansour A, Taylor-Weiner A, Rosenberg M et al (2014) Response and acquired resistance to everolimus in anaplastic thyroid cancer. N Engl J Med 371(15):1426–1433CrossRefPubMedPubMedCentral Wagle N, Grabiner BC, Van Allen EM, Amin-Mansour A, Taylor-Weiner A, Rosenberg M et al (2014) Response and acquired resistance to everolimus in anaplastic thyroid cancer. N Engl J Med 371(15):1426–1433CrossRefPubMedPubMedCentral
44.
Zurück zum Zitat Godbert Y, Henriques de Figueiredo B, Bonichon F, Chibon F, Hostein I, Perot G et al (2015) Remarkable response to Crizotinib in woman with anaplastic lymphoma kinase-rearranged anaplastic thyroid carcinoma. J Clin Oncol 33(20):e84–e87CrossRefPubMed Godbert Y, Henriques de Figueiredo B, Bonichon F, Chibon F, Hostein I, Perot G et al (2015) Remarkable response to Crizotinib in woman with anaplastic lymphoma kinase-rearranged anaplastic thyroid carcinoma. J Clin Oncol 33(20):e84–e87CrossRefPubMed
45.
Zurück zum Zitat Latteyer S, Tiedje V, Schilling B, Führer D (2016) Perspectives for immunotherapy in endocrine cancer. Endocr Relat Cancer 23(10):R469–84CrossRefPubMed Latteyer S, Tiedje V, Schilling B, Führer D (2016) Perspectives for immunotherapy in endocrine cancer. Endocr Relat Cancer 23(10):R469–84CrossRefPubMed
46.
Zurück zum Zitat Agrawal N, Jiao Y, Sausen M, Leary R, Bettegowda C, Roberts NJ, Bhan S, Ho AS, Khan Z, Bishop J, Westra WH, Wood LD, Hruban RH, Tufano RP, Robinson B, Dralle H, Toledo SP, Toledo RA, Morris LG, Ghossein RA, Fagin JA, Chan TA, Velculescu VE, Vogelstein B, Kinzler KW, Papadopoulos N, Nelkin BD, Ball DW (2013) Exomic sequencing of medullary thyroid cancer reveals dominant and mutually exclusive oncogenic mutations in RET and RAS. J Clin Endocrinol Metab 98(2):E364–E369CrossRefPubMed Agrawal N, Jiao Y, Sausen M, Leary R, Bettegowda C, Roberts NJ, Bhan S, Ho AS, Khan Z, Bishop J, Westra WH, Wood LD, Hruban RH, Tufano RP, Robinson B, Dralle H, Toledo SP, Toledo RA, Morris LG, Ghossein RA, Fagin JA, Chan TA, Velculescu VE, Vogelstein B, Kinzler KW, Papadopoulos N, Nelkin BD, Ball DW (2013) Exomic sequencing of medullary thyroid cancer reveals dominant and mutually exclusive oncogenic mutations in RET and RAS. J Clin Endocrinol Metab 98(2):E364–E369CrossRefPubMed
47.
Zurück zum Zitat Tiedje V, Ting S, Walter RF, Herold T, Worm K, Badziong J, Zwanziger D, Schmid KW, Führer D (2016) Prognostic markers and response to vandetanib therapy in sporadic medullary thyroid cancer patients. Eur J Endocrinol 175(3):173–180CrossRefPubMed Tiedje V, Ting S, Walter RF, Herold T, Worm K, Badziong J, Zwanziger D, Schmid KW, Führer D (2016) Prognostic markers and response to vandetanib therapy in sporadic medullary thyroid cancer patients. Eur J Endocrinol 175(3):173–180CrossRefPubMed
48.
Zurück zum Zitat Tiedje V, Ting S, Dralle H, Schmid KW, Führer D (2015) Medullary thyroid carcinoma. Internist (Berl) 56(9):1019–1031CrossRef Tiedje V, Ting S, Dralle H, Schmid KW, Führer D (2015) Medullary thyroid carcinoma. Internist (Berl) 56(9):1019–1031CrossRef
49.
Zurück zum Zitat Ting S, Schmid ST, Synoracki S, Schmid KW (2015) Thyroid C cells and their pathology: part 1: normal C cells,—C cell hyperplasia,—precursor of familial medullary thyroid carcinoma. Pathologe 36(6):571CrossRefPubMed Ting S, Schmid ST, Synoracki S, Schmid KW (2015) Thyroid C cells and their pathology: part 1: normal C cells,—C cell hyperplasia,—precursor of familial medullary thyroid carcinoma. Pathologe 36(6):571CrossRefPubMed
50.
Zurück zum Zitat Latteyer S, Klein-Hitpass L, Khandanpour C, Zwanziger D, Poeppel TD, Schmid KW, Führer D, Moeller LC (2016) A 6‑base pair in frame germline deletion in Exon 7 of RET leads to increased RET phosphorylation, ERK activation, and MEN2A. J Clin Endocrinol Metab 101(3):1016–1022CrossRefPubMed Latteyer S, Klein-Hitpass L, Khandanpour C, Zwanziger D, Poeppel TD, Schmid KW, Führer D, Moeller LC (2016) A 6‑base pair in frame germline deletion in Exon 7 of RET leads to increased RET phosphorylation, ERK activation, and MEN2A. J Clin Endocrinol Metab 101(3):1016–1022CrossRefPubMed
51.
Zurück zum Zitat Elisei R, Alevizaki M, Conte-Devolx B et al (2012) European Thyroid Association guidelines for genetic testing and its clinical consequences in medullary thyroid cancer. Eur Thyroid J 2012(1):216–231CrossRef Elisei R, Alevizaki M, Conte-Devolx B et al (2012) European Thyroid Association guidelines for genetic testing and its clinical consequences in medullary thyroid cancer. Eur Thyroid J 2012(1):216–231CrossRef
52.
Zurück zum Zitat Wells SA Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, Lee N, Machens A, Moley JF, Pacini F, Raue F, Frank-Raue K, Robinson B, Rosenthal MS, Santoro M, Schlumberger M, Shah M, Waguespack SG, American Thyroid Association Guidelines Task Force on Medullary Thyroid Carcinoma (2015) Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 25(6):567–610CrossRefPubMedPubMedCentral Wells SA Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, Lee N, Machens A, Moley JF, Pacini F, Raue F, Frank-Raue K, Robinson B, Rosenthal MS, Santoro M, Schlumberger M, Shah M, Waguespack SG, American Thyroid Association Guidelines Task Force on Medullary Thyroid Carcinoma (2015) Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 25(6):567–610CrossRefPubMedPubMedCentral
53.
Zurück zum Zitat Elisei R, Cosci B, Romei C, Bottici V, Renzini G, Molinaro E, Agate L, Vivaldi A, Faviana P, Basolo F, Miccoli P, Berti P, Pacini F, Pinchera A (2008) Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab 93(3):682–687CrossRefPubMed Elisei R, Cosci B, Romei C, Bottici V, Renzini G, Molinaro E, Agate L, Vivaldi A, Faviana P, Basolo F, Miccoli P, Berti P, Pacini F, Pinchera A (2008) Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab 93(3):682–687CrossRefPubMed
Metadaten
Titel
Genetik von Schilddrüsenknoten und Schilddrüsenkarzinomen
verfasst von
Prof. Dr. Dr. D. Führer
Publikationsdatum
21.06.2018
Verlag
Springer Medizin
Erschienen in
Die Innere Medizin / Ausgabe 7/2018
Print ISSN: 2731-7080
Elektronische ISSN: 2731-7099
DOI
https://doi.org/10.1007/s00108-018-0454-x

Weitere Artikel der Ausgabe 7/2018

Der Internist 7/2018 Zur Ausgabe

Mitteilungen des BDI

Mitteilungen des BDI

Passend zum Thema

ANZEIGE

AGO-Leitlinie 2024: Update zu CDK4 & 6 Inhibitoren

Die Kommission Mamma der Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) hat am 02. März 2024 ihre aktualisierten Empfehlungen präsentiert.[1,2] Welchen Stellenwert CDK4 & 6 Inhibitoren in der Therapie des Hormonrezeptor-positiven (HR+), HER2-negativen (HER2-) Mammakarzinoms haben, erfahren Sie hier im Update.

ANZEIGE

Finale OS-Analyse der MONARCH-3-Studie vorgestellt

In der MONARCH-3-Studie erhielten Patientinnen mit fortgeschrittenem HR+, HER2- Brustkrebs Abemaciclib [1,a] in Kombination mit nicht-steroidalem Aromatasehemmer (nsAI). Die finalen Daten bestätigen den in früheren Analysen beobachteten Unterschied zugunsten der Kombinationstherapie. [2] Details dazu vom SABCS 2023.

ANZEIGE

Die Bedeutung der CDK4 & 6 Inhibition beim HR+, HER2- Mammakarzinom

Es erwarten Sie praxisrelevante Patientenfälle, kompakte Studiendarstellungen, informative Experteninterviews sowie weitere spannende Inhalte rund um das HR+, HER2- Mammakarzinom.