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Pathogenesis of Thyroid Carcinoma

  • Massimo Santoro
  • Francesca Carlomagno
Reference work entry
Part of the Endocrinology book series (ENDOCR)

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.

Keywords

Kinase Neoplastic progression Differentiation MAPK TP53 TERT 

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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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Dipartimento di Medicina Molecolare e Biotecnologie MedicheUniversità di Napoli Federico IINaplesItaly

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