Luke K Genutis1, Jerneja Tomsic2, Ralf A Bundschuh3, Pamela L Brock4, Michelle D Williams5, Sameek Roychowdhury4, Julie W Reeser4, Wendy L Frankel6, Mohammed Alsomali6, Mark J Routbort7, Russell R Broaddus5, Paul E Wakely6, John E Phay8, Christopher J Walker1, Albert de la Chapelle1. 1. 1 Department of Cancer Biology and Genetics, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. 2. 2 Division of Biomarkers Early Detection Prevention, City of Hope Comprehensive Cancer Center, Duarte, California. 3. 3 Department of Physics and Department of Chemistry and Biochemistry, Division of Hematology, Department of Internal Medicine, Center for RNA Biology, The Ohio State University, Columbus, Ohio. 4. 4 Department of Internal Medicine, The Ohio State University, Columbus, Ohio. 5. 5 Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas. 6. 6 Department of Pathology, The Ohio State University, Columbus, Ohio. 7. 7 Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, Texas. 8. 8 Department of Surgery, The Ohio State University Wexner Medical Center, The Ohio State University, Columbus, Ohio.
Abstract
BACKGROUND: Inactivation of DNA mismatch repair (MMR) and the resulting microsatellite instability (MSI) are frequently observed in endometrial, stomach, and colorectal cancers, as well as more rarely in other solid tumor types. The prevalence of MSI in thyroid cancer has not been explored in depth, although recent studies utilizing data from large cancer sequencing efforts such as The Cancer Genome Atlas indicate that MSI is absent or at least very rare in the most common and most well studied histologic subtype, papillary thyroid carcinoma. This study aimed to determine the prevalence of MSI in thyroid cancer by using a large series comprising all major histological subtypes. METHODS: A total of 485 thyroid cancer patients were screened for MSI/MMR deficiency, including all major histologic subtypes (195 papillary thyroid carcinoma, 156 follicular thyroid carcinoma [FTC], 50 anaplastic thyroid carcinoma, 65 medullary thyroid carcinoma, and 17 poorly differentiated thyroid carcinomas) by using a combination of polymerase chain reaction-based detection, immunohistochemistry, and next-generation sequencing. RESULTS: A total of four tumors were MSI-high and had loss of MMR protein expression, all of which were from FTC patients. Whole-exome sequencing was performed on two MSI-high FTCs and revealed a hemizygous loss of function mutation in MSH2 in one tumor. CONCLUSIONS: Based on these data, it is estimated that the overall prevalence of MSI in FTC is 2.5%, and MSI is either entirely absent or rare in other histology subtypes of thyroid carcinoma. These findings highlight the importance of testing for MSI in FTC.
BACKGROUND: Inactivation of DNA mismatch repair (MMR) and the resulting microsatellite instability (MSI) are frequently observed in endometrial, stomach, and colorectal cancers, as well as more rarely in other solid tumor types. The prevalence of MSI in thyroid cancer has not been explored in depth, although recent studies utilizing data from large cancer sequencing efforts such as The Cancer Genome Atlas indicate that MSI is absent or at least very rare in the most common and most well studied histologic subtype, papillary thyroid carcinoma. This study aimed to determine the prevalence of MSI in thyroid cancer by using a large series comprising all major histological subtypes. METHODS: A total of 485 thyroid cancerpatients were screened for MSI/MMR deficiency, including all major histologic subtypes (195 papillary thyroid carcinoma, 156 follicular thyroid carcinoma [FTC], 50 anaplastic thyroid carcinoma, 65 medullary thyroid carcinoma, and 17 poorly differentiated thyroid carcinomas) by using a combination of polymerase chain reaction-based detection, immunohistochemistry, and next-generation sequencing. RESULTS: A total of four tumors were MSI-high and had loss of MMR protein expression, all of which were from FTC patients. Whole-exome sequencing was performed on two MSI-high FTCs and revealed a hemizygous loss of function mutation in MSH2 in one tumor. CONCLUSIONS: Based on these data, it is estimated that the overall prevalence of MSI in FTC is 2.5%, and MSI is either entirely absent or rare in other histology subtypes of thyroid carcinoma. These findings highlight the importance of testing for MSI in FTC.
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