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Pathogenesis of Thyroid Carcinoma

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Thyroid Diseases

Part of the book series: Endocrinology ((ENDOCR))

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Abstract

This chapter summarizes our current knowledge about molecular lesions driving the most common subtypes of thyroid carcinoma. Genetic lesions in the RET receptor tyrosine kinase and in RAS family GTPases are present in a large proportion of sporadic medullary thyroid carcinomas (MTC). RAS mutations are also common in well-differentiated thyroid carcinomas of the papillary (PTC) and follicular (FTC) type. Genetic lesions, most commonly the V600E point mutation, in the BRAF serine/threonine kinase are common in PTC; the PAX8-PPARG gene fusion is present in FTC. Finally, aggressive thyroid cancer types are enriched in several additional mutations including those targeting the TP53 tumor suppressor and the TERT (telomerase-reverse transcriptase) gene promoter. This knowledge is being translated into novel diagnostic and prognostic markers as well as molecular targets for novel therapeutic options.

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Abbreviations

4E-BP1:

4E-binding protein 1

AKT:

AKR mice tyhymoma oncogene

ALK:

Anaplastic lymphoma kinase

APC:

Adenomatous polyposis coli

ARID:

AT-rich interaction domain

ART:

Artemin

ATC:

Anaplastic thyroid carcinoma

ATRX:

ATP-dependent helicase X

BRAF:

B-type rapidly accelerated fibrosarcoma oncogene

CCDC6:

Coiled coil domain containing protein 6

CEA:

Carcinoembryonic antigen

CLA:

Cutaneous lichen amyloidosis

CLD:

Cadherin like domain

CRD:

Cysteine rich domain

CREBBP:

Cyclic AMP responsive element binding binding protein

CTNNB1:

Catenin beta 1

CV-PTC:

Classical variant-papillary thyroid carcinoma

DDR:

DNA damage response

DICER1:

Dicer 1 ribonuclease III

DTC:

Differentiated thyroid carcinoma

EIF1AX:

Eukaryotic translation initiation factor 1A, X-linked

ERK:

Extracellular regulated kinase

ETS:

E-twenty six

FAP:

Familial adenomatous polyposis of colon

FNMTC:

Familial non medullary thyroid carcinoma

FOXE1:

Forkhead box E1

FTA:

Follicular thyroid adenoma

FTC:

Follicular thyroid carcinoma

FTEN:

Familial thyroid epithelial neoplasia

FV-PTC:

Follicular variant-papillary thyroid carcinoma

GABP:

GA binding protein

GAP:

GTPase activating protein

GDNF:

Glial cell-derived neurotrophic factor

GEF:

Guanine nucleotide exchange factor

GTP:

Guanosine triphosphate

HCC:

Hürthle cell carcinoma

HD:

Hirschsprung's disease

Indels:

Insertion/deletions

KD:

Kinase domain

KMT2A/C/D:

Lysine methyltransferase 2 A/C/D

MAPK:

Mitogen-activated protein kinase

MEN:

Multiple endocrine neoplasia syndrome

MLH1:

Mut L homolog 1

MLH3:

Mut L homolog 3

MMR:

Mismatch repair

MNG1:

Multinodular goiter 1

MSH2:

Mut S homolog 2

MSH6:

Mut S homolog 6

MTC:

Medullary thyroid carcinoma

mTOR:

mammalian target of rapamycin

mTORC:

mammalian target of rapamycin complex

NCOA4:

Nuclear coactivator 4

NF1:

Neurofibromatosis 1

NF2:

Neurofibromatosis 2

NIFTP:

Non invasive follicular thyroid neoplasm with papillary like nuclear features

NKX2-1:

NK2 homeobox 1

NMTC:

Non-medullary thyroid carcinoma

NMTC1:

Non-medullary thyroid carcinoma 1

NRT:

Neurturin

NTRK:

Neurotrophic tyrosine kinase

PAX8:

Paired box gene 8

PBMR1:

Polybromo-1, BRG1-associated factor

PDK1:

Phosphoinositide-dependent kinase 1

PDTC:

Poorly differentiated thyroid carcinoma

PI3K:

Phosphatidylinositol 3 kinase

PI3KCA:

Phosphatidylinositol 3 kinase catalytic subunit

PIP3:

Phosphatidylinositol (3,4,5)-trisphosphate

PKB:

Protein kinase B

PPARG:

Peroxisome proliferator-activated receptor gamma

PPFP:

PAX8-PPARG fusion protein

PSP:

Persephin

PTC:

Papillary thyroid carcinoma

PTEN:

Phosphatase and tensin homolog

RAS:

Rat sarcoma oncogene

RBD:

Ras binding domain

RET:

Rearranged during transfection

RSK:

Ribosomal protein S6 kinase

RTK:

Receptor tyrosine kinase

SBS:

Single base substitution

SETD2:

SET domain containing 2 protein

SMARCB1:

SWI/SNF related matrix associated actin dependent regulator of chromatin B1

SOS:

Son of sevenless

SWI/SNF:

SwItch/sucrose non-fermentable

TC:

Thyroid carcinoma

TCGA:

The cancer genome atlas

TCO:

Thyroid tumors with cell oxyphilia

TCV-PTC:

Tall cell variant-papillary thyroid carcinoma

TERT:

Telomerase reverse transcriptase

THADA:

Thyroid adenoma associated protein

TP53:

Tumor protein p53

TSC2:

Tuberous sclerosis 2

TSH:

Thyroid stimulating hormone

WNT:

Wingless-related integration site

YAP:

Yes-associated protein

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Authors and Affiliations

  1. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Via S Pansini 5, 80131, Naples, Italy

    Massimo Santoro & Francesca Carlomagno

Authors
  1. Massimo Santoro
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  2. Francesca Carlomagno
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Correspondence to Massimo Santoro .

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Editors and Affiliations

  1. Department of Endocrinology, University of Pisa, Pisa, Italy

    Paolo Vitti

  2. Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark

    Laszlo Hegedüs

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Santoro, M., Carlomagno, F. (2018). Pathogenesis of Thyroid Carcinoma. In: Vitti, P., Hegedüs, L. (eds) Thyroid Diseases. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-45013-1_20

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  • DOI: https://doi.org/10.1007/978-3-319-45013-1_20

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-45012-4

  • Online ISBN: 978-3-319-45013-1

  • eBook Packages: MedicineReference Module Medicine

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