Clinical and molecular characterization of thyroid cancer when seen as a second malignant neoplasm

Background: Second malignant neoplasms (SMN) are among the most serious long-term adverse health conditions in cancer survivors. The aim of this study was to characterize clinical findings of patients who developed thyroid cancers as SMN, and to examine genomic alterations in thyroid cancer tissue....

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Autores principales:	Kristen Romanelli, Justin Wells, Aneeta Patel, Maria Mendonca Torres, John Costello, Kirk Jensen, Vasyl Vasko
Formato:	article
Lenguaje:	EN
Publicado:	SAGE Publishing 2021
Materias:	Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/15c8db2c2ab54d238316cb7fb8854014
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spelling	oai:doaj.org-article:15c8db2c2ab54d238316cb7fb88540142021-12-01T00:05:41ZClinical and molecular characterization of thyroid cancer when seen as a second malignant neoplasm2042-019610.1177/20420188211058327https://doaj.org/article/15c8db2c2ab54d238316cb7fb88540142021-11-01T00:00:00Zhttps://doi.org/10.1177/20420188211058327https://doaj.org/toc/2042-0196Background: Second malignant neoplasms (SMN) are among the most serious long-term adverse health conditions in cancer survivors. The aim of this study was to characterize clinical findings of patients who developed thyroid cancers as SMN, and to examine genomic alterations in thyroid cancer tissue. Methods: Retrospective analysis of medical records from patients seen for management of thyroid cancer over 10-year period was performed. Clinical and pathologic data were retrieved from their medical charts. Tumor DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and subjected to next-generation sequencing (NGS) using Ion Torrent Oncomine Focus Assay. Microfluidic digital polymerase chain reactions (PCRs) were performed using QIAcuity Digital PCR System to identify BRAF V600E mutations and RET/PTC fusions. Results: Sixteen of 620 patients operated for thyroid cancer had history of previously diagnosed malignancy. Eight patients were male and eight patients were female, with a median age at diagnosis of 58.5 years (range, 4–78). Four patients had history of pediatric malignancy (PedCa), and 12 patients had a history of prior malignancy as an adult (AdCa). The latency periods for development of SMN in PedCa and AdCa patients were 10.8 (±5.2) years and 9.5 (±5.2) years, respectively. Histopathology revealed papillary thyroid cancers in 15 cases, and follicular thyroid cancer in 1 case. All tumors were classified as T1 or T2, and there were no patients presenting with metastases at the time of surgery. Genomic alterations were detected in 13/16 (81.2%) tumors including eight gene mutations ( BRAF V600E (N = 4), RAS (N = 2), PI3CA (N = 2) and five gene fusions ( RET/PTC1 (N = 4) and STRN/ALK (N = 1). In patients with PedCa and AdCa, mutations were detected in 1/4 (25%) and 7/12 (58.3%), respectively, p = 0.56; and fusions were detected in 3/4 (75%) and 2/12 (16.6%), respectively, p = 0.06. In patients with and without history of therapeutic irradiation, mutations were detected with the same frequencies (5/10 (50%), and 3/6 (50%), respectively, p = 1.0). Gene fusions were detected in patients with and without history of irradiation in 5/10 (55.5%) and 0/6 (0%), respectively, p = 0.09. Conclusions: Monitoring of cancer survivors for thyroid disorders allowed diagnosis of second thyroid cancers at early stages. Second thyroid cancers harbor genomic alterations that are typical for sporadic as well as for radio-induced thyroid cancers.Kristen RomanelliJustin WellsAneeta PatelMaria Mendonca TorresJohn CostelloKirk JensenVasyl VaskoSAGE PublishingarticleDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENTherapeutic Advances in Endocrinology and Metabolism, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	Diseases of the endocrine glands. Clinical endocrinology RC648-665 Kristen Romanelli Justin Wells Aneeta Patel Maria Mendonca Torres John Costello Kirk Jensen Vasyl Vasko Clinical and molecular characterization of thyroid cancer when seen as a second malignant neoplasm
description	Background: Second malignant neoplasms (SMN) are among the most serious long-term adverse health conditions in cancer survivors. The aim of this study was to characterize clinical findings of patients who developed thyroid cancers as SMN, and to examine genomic alterations in thyroid cancer tissue. Methods: Retrospective analysis of medical records from patients seen for management of thyroid cancer over 10-year period was performed. Clinical and pathologic data were retrieved from their medical charts. Tumor DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and subjected to next-generation sequencing (NGS) using Ion Torrent Oncomine Focus Assay. Microfluidic digital polymerase chain reactions (PCRs) were performed using QIAcuity Digital PCR System to identify BRAF V600E mutations and RET/PTC fusions. Results: Sixteen of 620 patients operated for thyroid cancer had history of previously diagnosed malignancy. Eight patients were male and eight patients were female, with a median age at diagnosis of 58.5 years (range, 4–78). Four patients had history of pediatric malignancy (PedCa), and 12 patients had a history of prior malignancy as an adult (AdCa). The latency periods for development of SMN in PedCa and AdCa patients were 10.8 (±5.2) years and 9.5 (±5.2) years, respectively. Histopathology revealed papillary thyroid cancers in 15 cases, and follicular thyroid cancer in 1 case. All tumors were classified as T1 or T2, and there were no patients presenting with metastases at the time of surgery. Genomic alterations were detected in 13/16 (81.2%) tumors including eight gene mutations ( BRAF V600E (N = 4), RAS (N = 2), PI3CA (N = 2) and five gene fusions ( RET/PTC1 (N = 4) and STRN/ALK (N = 1). In patients with PedCa and AdCa, mutations were detected in 1/4 (25%) and 7/12 (58.3%), respectively, p = 0.56; and fusions were detected in 3/4 (75%) and 2/12 (16.6%), respectively, p = 0.06. In patients with and without history of therapeutic irradiation, mutations were detected with the same frequencies (5/10 (50%), and 3/6 (50%), respectively, p = 1.0). Gene fusions were detected in patients with and without history of irradiation in 5/10 (55.5%) and 0/6 (0%), respectively, p = 0.09. Conclusions: Monitoring of cancer survivors for thyroid disorders allowed diagnosis of second thyroid cancers at early stages. Second thyroid cancers harbor genomic alterations that are typical for sporadic as well as for radio-induced thyroid cancers.
format	article
author	Kristen Romanelli Justin Wells Aneeta Patel Maria Mendonca Torres John Costello Kirk Jensen Vasyl Vasko
author_facet	Kristen Romanelli Justin Wells Aneeta Patel Maria Mendonca Torres John Costello Kirk Jensen Vasyl Vasko
author_sort	Kristen Romanelli
title	Clinical and molecular characterization of thyroid cancer when seen as a second malignant neoplasm
title_short	Clinical and molecular characterization of thyroid cancer when seen as a second malignant neoplasm
title_full	Clinical and molecular characterization of thyroid cancer when seen as a second malignant neoplasm
title_fullStr	Clinical and molecular characterization of thyroid cancer when seen as a second malignant neoplasm
title_full_unstemmed	Clinical and molecular characterization of thyroid cancer when seen as a second malignant neoplasm
title_sort	clinical and molecular characterization of thyroid cancer when seen as a second malignant neoplasm
publisher	SAGE Publishing
publishDate	2021
url	https://doaj.org/article/15c8db2c2ab54d238316cb7fb8854014
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Clinical and molecular characterization of thyroid cancer when seen as a second malignant neoplasm

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