TY - JOUR
T1 - Microsatellite Instability Occurs in a Subset of Follicular Thyroid Cancers
AU - Genutis, Luke K.
AU - Tomsic, Jerneja
AU - Bundschuh, Ralf A.
AU - Brock, Pamela L.
AU - Williams, Michelle D.
AU - Roychowdhury, Sameek
AU - Reeser, Julie W.
AU - Frankel, Wendy L.
AU - Alsomali, Mohammed
AU - Routbort, Mark J.
AU - Broaddus, Russell R.
AU - Wakely, Paul E.
AU - Phay, John E.
AU - Walker, Christopher J.
AU - De La Chapelle, Albert
N1 - Funding Information:
The authors would like to acknowledge: the patients who consented to provide material for this study; Jan Lockman and Barbara Fersch for administrative help; the OSUCCC Genomics Shared Resource and the Plant Microbe Genomics Facility for sequencing assistance; the OSUCCC Human Cancer Genetics Sample Bank for sample processing and storage; and the Ohio Supercomputer Center for computational resources. This work was supported by the Leukemia Clinical Research Foundation, the Pelotonia fellowship program, and the National Cancer Institute Grants P01CA124570 and P50CA 168505.
Publisher Copyright:
© 2019, Mary Ann Liebert, Inc., publishers.
PY - 2019/4
Y1 - 2019/4
N2 - 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.
AB - 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.
KW - DNA mismatch repair
KW - Lynch syndrome
KW - Microsatellite instability
KW - follicular thyroid cancer
KW - papillary thyroid carcinoma
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U2 - 10.1089/thy.2018.0655
DO - 10.1089/thy.2018.0655
M3 - Article
C2 - 30747051
AN - SCOPUS:85064206014
SN - 1050-7256
VL - 29
SP - 523
EP - 529
JO - Thyroid
JF - Thyroid
IS - 4
ER -