Abstract
Background: Papillary Thyroid Carcinomas (PTCs) are generally indolent tumors. However, a small but significant percentage of PTCs behaves aggressively, progressing to a diffuse metastatic spreading and leading to patient's death. The lack of reliable markers for predicting the metastatic behavior of these tumors prevents a correct risk based stratification of the disease, thus contributing to the issue of patients' overtreatment. In this study we aimed at identifying genetic features associated with the development of distant metastasis in PTCs. Results: We showed that DM PTCs are characterized by a moderate degree of copy number alterations but display low level of microsatellite instability and a low mutational burden. We identified duplication of Chr1q, duplication of Chr5p harboring the TERT genomic locus and mutations of TERT promoter as distinctive features of DM PTCs. These three genetic variables defined a signature (THYT1) that was significantly associated with a metastatic behavior and a shortened survival. We analyzed the THYT1 signature in PTCs fine needle aspirate biopsies (FNAB) and we demonstrating the applicability of this signature as a molecular marker in the pre-operative diagnostic setting of PTCs. Materials and Methods: A consecutive series of 2,937 thyroid malignancies, diagnosed at the Arcispedale S. Maria Nuova - IRCCS, Italy between 1978 and 2015 were searched to retrieve those who developed distant metastasis (DM, n = 50). We performed a deep profiling to explore the genomic landscape of these tumors. Conclusions: Overall our data identify the first genetic signature that independently predicts metastasis and negative outcome of PTCs, and lay the basis for the possible application of the THYT1 as prognostic marker to improve risk-based stratification and management of PTC patients.
| Original language | English |
|---|---|
| Pages (from-to) | 1813-1825 |
| Number of pages | 13 |
| Journal | Oncotarget |
| Volume | 9 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 1 2018 |
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Keywords
- Copy number alterations
- Distant metastases
- Next generation sequencing
- Papillary thyroid carcinomas
- TERT duplication
ASJC Scopus subject areas
- Oncology
Cite this
Genome-wide profiling identifies the THYT1 signature as a distinctive feature of widely metastatic Papillary Thyroid Carcinomas. / Gandolfi, Greta; Ragazzi, Moira; de Biase, Dario; Visani, Michela; Zanetti, Eleonora; Torricelli, Federica; Sancisi, Valentina; Gugnoni, Mila; Manzotti, Gloria; Braglia, Luca; Cavuto, Silvio; Merlo, Domenico Franco; Tallini, Giovanni; Frasoldati, Andrea; Piana, Simonetta; Ciarrocchi, Alessia.
In: Oncotarget, Vol. 9, No. 2, 01.01.2018, p. 1813-1825.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genome-wide profiling identifies the THYT1 signature as a distinctive feature of widely metastatic Papillary Thyroid Carcinomas
AU - Gandolfi, Greta
AU - Ragazzi, Moira
AU - de Biase, Dario
AU - Visani, Michela
AU - Zanetti, Eleonora
AU - Torricelli, Federica
AU - Sancisi, Valentina
AU - Gugnoni, Mila
AU - Manzotti, Gloria
AU - Braglia, Luca
AU - Cavuto, Silvio
AU - Merlo, Domenico Franco
AU - Tallini, Giovanni
AU - Frasoldati, Andrea
AU - Piana, Simonetta
AU - Ciarrocchi, Alessia
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Background: Papillary Thyroid Carcinomas (PTCs) are generally indolent tumors. However, a small but significant percentage of PTCs behaves aggressively, progressing to a diffuse metastatic spreading and leading to patient's death. The lack of reliable markers for predicting the metastatic behavior of these tumors prevents a correct risk based stratification of the disease, thus contributing to the issue of patients' overtreatment. In this study we aimed at identifying genetic features associated with the development of distant metastasis in PTCs. Results: We showed that DM PTCs are characterized by a moderate degree of copy number alterations but display low level of microsatellite instability and a low mutational burden. We identified duplication of Chr1q, duplication of Chr5p harboring the TERT genomic locus and mutations of TERT promoter as distinctive features of DM PTCs. These three genetic variables defined a signature (THYT1) that was significantly associated with a metastatic behavior and a shortened survival. We analyzed the THYT1 signature in PTCs fine needle aspirate biopsies (FNAB) and we demonstrating the applicability of this signature as a molecular marker in the pre-operative diagnostic setting of PTCs. Materials and Methods: A consecutive series of 2,937 thyroid malignancies, diagnosed at the Arcispedale S. Maria Nuova - IRCCS, Italy between 1978 and 2015 were searched to retrieve those who developed distant metastasis (DM, n = 50). We performed a deep profiling to explore the genomic landscape of these tumors. Conclusions: Overall our data identify the first genetic signature that independently predicts metastasis and negative outcome of PTCs, and lay the basis for the possible application of the THYT1 as prognostic marker to improve risk-based stratification and management of PTC patients.
AB - Background: Papillary Thyroid Carcinomas (PTCs) are generally indolent tumors. However, a small but significant percentage of PTCs behaves aggressively, progressing to a diffuse metastatic spreading and leading to patient's death. The lack of reliable markers for predicting the metastatic behavior of these tumors prevents a correct risk based stratification of the disease, thus contributing to the issue of patients' overtreatment. In this study we aimed at identifying genetic features associated with the development of distant metastasis in PTCs. Results: We showed that DM PTCs are characterized by a moderate degree of copy number alterations but display low level of microsatellite instability and a low mutational burden. We identified duplication of Chr1q, duplication of Chr5p harboring the TERT genomic locus and mutations of TERT promoter as distinctive features of DM PTCs. These three genetic variables defined a signature (THYT1) that was significantly associated with a metastatic behavior and a shortened survival. We analyzed the THYT1 signature in PTCs fine needle aspirate biopsies (FNAB) and we demonstrating the applicability of this signature as a molecular marker in the pre-operative diagnostic setting of PTCs. Materials and Methods: A consecutive series of 2,937 thyroid malignancies, diagnosed at the Arcispedale S. Maria Nuova - IRCCS, Italy between 1978 and 2015 were searched to retrieve those who developed distant metastasis (DM, n = 50). We performed a deep profiling to explore the genomic landscape of these tumors. Conclusions: Overall our data identify the first genetic signature that independently predicts metastasis and negative outcome of PTCs, and lay the basis for the possible application of the THYT1 as prognostic marker to improve risk-based stratification and management of PTC patients.
KW - Copy number alterations
KW - Distant metastases
KW - Next generation sequencing
KW - Papillary thyroid carcinomas
KW - TERT duplication
UR - http://www.scopus.com/inward/record.url?scp=85039984788&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85039984788&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.22805
DO - 10.18632/oncotarget.22805
M3 - Article
VL - 9
SP - 1813
EP - 1825
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 2
ER -