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Differential Gene Expression of Medullary Thyroid Carcinoma Reveals Specific Markers Associated with Genetic Conditions
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2013
- Publisher :
- American Society for Investigative Pathology, 2013.
-
Abstract
- Maliszewska, Agnieszka et al.<br />Medullary thyroid carcinoma accounts for 2% to 5% of thyroid malignancies, of which 75% are sporadic and the remaining 25% are hereditary and related to multiple endocrine neoplasia type 2 syndrome. Despite a genotype-phenotype correlation with specific germline RET mutations, knowledge of pathways specifically associated with each mutation and with non-RET-mutated sporadic MTC remains lacking. Gene expression patterns have provided a tool for identifying molecular events related to specific tumor types and to different clinical features that could help identify novel therapeutic targets. Using transcriptional profiling of 49 frozen MTC specimens classified as RET mutation, we identified PROM1, LOXL2, GFRA1, and DKK4 as related to RETM918T and GAL as related to RET634 mutation. An independent series of 19 frozen and 23 formalin-fixed, paraffin-embedded (FFPE) MTCs was used for validation by RT-qPCR. Two tissue microarrays containing 69 MTCs were available for IHC assays. According to pathway enrichment analysis and gene ontology biological processes, genes associated with the MTCM918T group were involved mainly in proliferative, cell adhesion, and general malignant metastatic effects and with Wnt, Notch, NFκB, JAK/Stat, and MAPK signaling pathways. Assays based on silencing of PROM1 by siRNAs performed in the MZ-CRC-1 cell line, harboring RETM918T, caused an increase in apoptotic nuclei, suggesting that PROM1 is necessary for survival of these cells. This is the first report of PROM1 overexpression among primary tumors.<br />MZ-CRC-1 cells were a generous gift of Dr. Robert F. Gagel (MD Anderson Cancer Center, University of Texas, Houston, TX).
- Subjects :
- Pathology
medicine.medical_specialty
endocrine system diseases
Inheritance Patterns
Multiple endocrine neoplasia type 2
Apoptosis
Biology
Germline
Pathology and Forensic Medicine
Thyroid carcinoma
Antigens, CD
Cell Line, Tumor
medicine
Biomarkers, Tumor
Gene silencing
Cluster Analysis
Humans
Genetic Predisposition to Disease
AC133 Antigen
Gene Silencing
Thyroid Neoplasms
RNA, Small Interfering
Glycoproteins
Regulation of gene expression
Tissue microarray
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
Wnt signaling pathway
medicine.disease
Immunohistochemistry
Carcinoma, Neuroendocrine
Gene expression profiling
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Cancer research
Peptides
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Accession number :
- edsair.doi.dedup.....8b24724bd74bcebed893cddd22046540