TY - JOUR
T1 - Intratumoral genetic heterogeneity in papillary thyroid cancer
T2 - Occurrence and clinical significance
AU - Fugazzola, Laura
AU - Muzza, Marina
AU - Pogliaghi, Gabriele
AU - Vitale, Mario
N1 - Funding Information:
Funding: This work was partially supported by the RicercaFinalizzata program of Italian Ministry of Health, Rome (code: RF 2013-02354985) and by the Ministerodell'Istruzione, dell'Università e dellaRicerca (MIUR, Investigator Grant 2015, PRIN 2017YTWKWH).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/2
Y1 - 2020/2
N2 - Intratumoral heterogeneity (ITH) refers to a subclonal genetic diversity observed within a tumor. ITH is the consequence of genetic instability and accumulation of genetic alterations, two mechanisms involved in the progression from an early tumor stage to a more aggressive cancer. While this process is widely accepted, the ITH of early stage papillary thyroid carcinoma (PTC) is debated. By different genetic analysis, several authors reported the frequent occurrence of PTCs composed of both tumor cells with and without RET/PTC or BRAFV600E genetic alterations. While these data, and the report of discrepancies in the genetic pattern between metastases and the primary tumor, demonstrate the existence of ITH in PTC, its extension and biological significance is debated. The ITH takes on a great significance when involves oncogenes, such as RET rearrangements and BRAFV600E as it calls into question their role of driver genes. ITH is also predicted to play a major clinical role as it could have a significant impact on prognosis and on the response to targeted therapy. In this review, we analyzed several data indicating that ITH is not a marginal event, occurring in PTC at any step of development, and suggesting the existence of unknown genetic or epigenetic alterations that still need to be identified.
AB - Intratumoral heterogeneity (ITH) refers to a subclonal genetic diversity observed within a tumor. ITH is the consequence of genetic instability and accumulation of genetic alterations, two mechanisms involved in the progression from an early tumor stage to a more aggressive cancer. While this process is widely accepted, the ITH of early stage papillary thyroid carcinoma (PTC) is debated. By different genetic analysis, several authors reported the frequent occurrence of PTCs composed of both tumor cells with and without RET/PTC or BRAFV600E genetic alterations. While these data, and the report of discrepancies in the genetic pattern between metastases and the primary tumor, demonstrate the existence of ITH in PTC, its extension and biological significance is debated. The ITH takes on a great significance when involves oncogenes, such as RET rearrangements and BRAFV600E as it calls into question their role of driver genes. ITH is also predicted to play a major clinical role as it could have a significant impact on prognosis and on the response to targeted therapy. In this review, we analyzed several data indicating that ITH is not a marginal event, occurring in PTC at any step of development, and suggesting the existence of unknown genetic or epigenetic alterations that still need to be identified.
KW - BRAF 3
KW - Clonality
KW - Heterogeneity
KW - RET/PTC
KW - Thyroid cancer
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U2 - 10.3390/cancers12020383
DO - 10.3390/cancers12020383
M3 - Review article
AN - SCOPUS:85079126968
VL - 12
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 2
M1 - 383
ER -