Abstract
Alterations in the switching defective/sucrose non-fermenting (SWI/SNF) chromatin-remodeling complex are enriched in advanced thyroid cancer. Integrase interactor 1 (INI1), encoded by the SMARCB1 gene on the long arm of chromosome 22, is one of the core subunits of the SWI/SNF complex. INI1 immunohistochemistry is frequently used for the diagnosis of malignant rhabdoid neoplasms. In the present study, we found normal and benign thyroid tissues generally had diffusely intense nuclear immunostaining. Loss of INI1 immunohistochemical expression was observed in 8% of papillary thyroid cancer and 30% of follicular thyroid cancer. Furthermore, loss of INI1 expression was associated with extrathyroidal extension (p < 0.001) and lymph node metastasis (p = 0.038). Analysis of The Cancer Genome Atlas database revealed that SMARCB1 underexpression was associated with the follicular variant subtype and aneuploidy in papillary thyroid cancer. We speculate that SMARCB1 is an important effector in addition to NF2 and CHEK2 inactivation among thyroid cancers with chromosome 22q loss.
Highlights
Thyroid cancer has a wide spectrum of different morphologies and clinical behaviors, ranging from indolent differentiated thyroid cancer to aggressive and invariably lethal anaplastic cancer
Alterations in switching defective/sucrose non-fermenting (SWI/SNF) complex, mismatch repair genes, and histone methyltransferases were found as novel mechanisms and therapeutic targets in advanced thyroid cancer [2]
To preliminarily assess whether SMARCB1 was differentially expressed in thyroid cancer, we Results examined a microarray dataset downloaded from
Summary
Thyroid cancer has a wide spectrum of different morphologies and clinical behaviors, ranging from indolent differentiated thyroid cancer to aggressive and invariably lethal anaplastic cancer. Differentiated thyroid cancer takes an intermediate position on the progression spectrum. Along the process of dedifferentiation, activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway has long been recognized as a key molecular event [1]. Alterations in switching defective/sucrose non-fermenting (SWI/SNF) complex, mismatch repair genes, and histone methyltransferases were found as novel mechanisms and therapeutic targets in advanced thyroid cancer [2]. SWI/SNF chromatin-remodeling complex consists of multiple subunits and regulates transcriptional activity by binding to promoters or other regulatory regions. Depending on whether a transcriptional activator or repressor recruits SWI/SNF, transcription can be upregulated or downregulated.
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