Gene Expression Profiles for Radiation-induced Thyroid Cancer

PurposeFibroblasts are considered to play a major role in the development of fibrotic reaction after radiotherapy and premature radiation-induced differentiation has been proposed as a cellular basis. The purpose was to relate gene expression profiles to radiation-induced phenotypic changes of human skin fibroblasts relevant for radiogenic fibrosis.Materials and MethodsExponentially growing or confluent human skin fibroblast strains were irradiated in vitro with 1–3 fractions of 4 Gy X-rays. The differentiated phenotype was detected by cytomorphological scoring and immunofluorescence microscopy. Microarray analysis was performed on Human Genome U133 plus2.0 microarrays (Affymetrix) with JMP Genomics software, and pathway analysis with Reactome R-package. The expression levels and kinetics of selected genes were validated with quantitative real-time PCR (qPCR) and Western blotting.ResultsIrradiation of exponentially growing fibroblast with 1 × 4 Gy resulted in phenotypic differentiation over a 5-day period. This was accompanied by downregulation of cell cycle-related genes and upregulation of collagen and other extracellular matrix (ECM)-related genes. Pathway analysis confirmed inactivation of proliferation and upregulation of ECM- and glycosaminoglycan (GAG)-related pathways. Furthermore, pathways related to inflammatory reactions were upregulated, and potential induction and signaling mechanisms were identified. Fractionated irradiation (3 × 4 Gy) of confluent cultures according to a previously published protocol for predicting the risk of fibrosis after radiotherapy showed similar downregulation but differences in upregulated genes and pathways.ConclusionGene expression profiles after irradiation of exponentially growing cells were related to radiation-induced differentiation and inflammatory reactions, and potential signaling mechanisms. Upregulated pathways by different irradiation protocols may reflect different aspects of the fibrogenic process thus providing a model system for further hypothesis-based studies of radiation-induced fibrogenesis.

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Radiation-Induced Changes in Gene-Expression Profiles for the SCC VII Tumor Cells Grown In Vitro and In Vivo

Antioxidants and Redox Signaling ◽

10.1089/ars.2006.8.1263 ◽

2006 ◽

Vol 8 (7-8) ◽

pp. 1263-1272 ◽

Cited By ~ 7

Author(s):

John A. Cook ◽

Eric Y. Chuang ◽

Mong-Hsun Tsai ◽

Debbie Coffin ◽

William Degraff ◽

...

Keyword(s):

Gene Expression ◽

Tumor Cells ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Radiation Induced ◽

Induced Changes

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Gene Expression Profiles from Heart, Lung and Liver Samples of Total-Body-Irradiated Minipigs: Implications for Predicting Radiation-Induced Tissue Toxicity

Radiation Research ◽

10.1667/rade-20-00123.1 ◽

2020 ◽

Vol 194 (4) ◽

Author(s):

Sunita Chopra ◽

Maria Moroni ◽

Shannon Martello ◽

Michelle Bylicky ◽

Jared May ◽

...

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Radiation Induced ◽

Total Body

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Differences in the transcriptome of medullary thyroid cancer regarding the status and type of RET gene mutations

Scientific Reports ◽

10.1038/srep42074 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 11

Author(s):

Malgorzata Oczko-Wojciechowska ◽

Michal Swierniak ◽

Jolanta Krajewska ◽

Malgorzata Kowalska ◽

Monika Kowal ◽

...

Keyword(s):

Gene Expression ◽

Thyroid Cancer ◽

Gene Mutation ◽

Gene Expression Profile ◽

Expression Profile ◽

Medullary Thyroid Cancer ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Tumour Suppressor Gene ◽

Medullary Thyroid

Abstract Medullary thyroid cancer (MTC) can be caused by germline mutations of the RET proto-oncogene or occurs as a sporadic form. It is well known that RET mutations affecting the cysteine-rich region of the protein (MEN2A-like mutations) are correlated with different phenotypes than those in the kinase domain (MEN2B-like mutations). Our aim was to analyse the whole-gene expression profile of MTC with regard to the type of RET gene mutation and the cancer genetic background (hereditary vs sporadic). We studied 86 MTC samples. We demonstrated that there were no distinct differences in the gene expression profiles of hereditary and sporadic MTCs. This suggests a homogeneous nature of MTC. We also noticed that the site of the RET gene mutation slightly influenced the gene expression profile of MTC. We found a significant association between the localization of RET mutations and the expression of three genes: NNAT (suggested to be a tumour suppressor gene), CDC14B (involved in cell cycle control) and NTRK3 (tyrosine receptor kinase that undergoes rearrangement in papillary thyroid cancer). This study suggests that these genes are significantly deregulated in tumours with MEN2A-like and MEN2B-like mutations; however, further investigations are necessary to demonstrate any clinical impact of these findings.

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Genomic Dissection of Hurthle Cell Carcinoma Reveals a Unique Class of Thyroid Malignancy

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2012-3539 ◽

2013 ◽

Vol 98 (5) ◽

pp. E962-E972 ◽

Cited By ~ 111

Author(s):

Ian Ganly ◽

Julio Ricarte Filho ◽

Stephanie Eng ◽

Ronald Ghossein ◽

Luc G. T. Morris ◽

...

Keyword(s):

Gene Expression ◽

Thyroid Cancer ◽

Cell Carcinoma ◽

Copy Number ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Follicular Thyroid Cancer ◽

Hürthle Cell ◽

Hürthle Cell Carcinoma ◽

Hurthle Cell Carcinoma

Context: Hurthle cell cancer (HCC) is an understudied cancer with poor prognosis. Objective: Our objective was to elucidate the genomic foundations of HCC. Design and Setting: We conducted a large-scale integrated analysis of mutations, gene expression profiles, and copy number alterations in HCC at a single tertiary-care cancer institution. Methods: Mass spectrometry-based genotyping was used to interrogate hot spot point mutations in the most common thyroid oncogenes: BRAF, RET, NRAS, HRAS, KRAS, PIK3CA, MAP2K1, and AKT1. In addition, common oncogenic fusions of RET and NTRK1 as well as PAX8/PPARγ and AKAP9-BRAF were also assessed by RT-PCR. Global copy number changes and gene expression profiles were determined in the same tumor set as the mutational analyses. Results: We report that the mutational, transcriptional, and copy number profiles of HCC were distinct from those of papillary thyroid cancer and follicular thyroid cancer, indicating HCC to be a unique type of thyroid malignancy. Unsupervised hierarchical clustering of gene expression showed the 3 groups of Hurthle tumors (Hurthle cell adenoma [HA], minimally invasive Hurthle cell carcinoma [HMIN], and widely invasive Hurthle cell carcinoma [HWIDE] clustered separately with a marked difference between HWIDE and HA. Global copy number analysis also indicated distinct subgroups of tumors that may arise as HWIDE and HMIN. Molecular pathways that differentiate HA from HWIDE included the PIK3CA-Akt-mTOR and Wnt/β-catenin pathways, potentially providing a rationale for new targets for this type of malignancy. Conclusions: Our data provide evidence that HCC may be a unique thyroid cancer distinct from papillary and follicular thyroid cancer.

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