TY - JOUR
T1 - Variability in Medullary Thyroid Carcinoma in RET L790F Carriers
T2 - A Case Comparison Study of Index Patients
AU - Mathiesen, Jes Sloth
AU - Nielsen, Søren Grønlund
AU - Rasmussen, Åse Krogh
AU - Kiss, Katalin
AU - Wadt, Karin
AU - Hermann, Anne Pernille
AU - Nielsen, Morten Frost
AU - Larsen, Stine Rosenkilde
AU - Brusgaard, Klaus
AU - Frederiksen, Anja Lisbeth
AU - Godballe, Christian
AU - Rossing, Maria
PY - 2020/4/28
Y1 - 2020/4/28
N2 - Background: Previous studies have suggested that the variability in age of onset and aggressiveness of medullary thyroid carcinoma (MTC) in patients with multiple endocrine neoplasia type 2A (MEN 2A) carrying the same REarranged during Transfection (RET) mutation may be caused by additional RET germline variants or somatic variants. Methods: This study was a retrospective case comparison study of all MEN 2A index patients (n = 2) with the RET L790F germline mutation in Denmark. Whole blood and MTC tissue were analyzed for RET germline variants and other somatic variants (>500), respectively. Results: Patient 1 presented with MTC (T1aN1bM0) at age 14 years, while patient 2 presented with MTC (T1bN0M0) at age 70 years. No germline RET germline variants nor other variants were found to explain this MTC variability. Conclusions: We could not confirm the previously reported finding of a somatic RET variant as likely responsible for the early onset and aggressiveness of MTC in a RET germline mutation carrier. Also, we found no RET germline variants that could explain the MTC variability among our index patients. We did, however, identify a somatic FLT3 R387Q variant with an unknown potential as genetic modifier. Further large-scale studies are needed to investigate genetic modifiers in RET L790F carriers.
AB - Background: Previous studies have suggested that the variability in age of onset and aggressiveness of medullary thyroid carcinoma (MTC) in patients with multiple endocrine neoplasia type 2A (MEN 2A) carrying the same REarranged during Transfection (RET) mutation may be caused by additional RET germline variants or somatic variants. Methods: This study was a retrospective case comparison study of all MEN 2A index patients (n = 2) with the RET L790F germline mutation in Denmark. Whole blood and MTC tissue were analyzed for RET germline variants and other somatic variants (>500), respectively. Results: Patient 1 presented with MTC (T1aN1bM0) at age 14 years, while patient 2 presented with MTC (T1bN0M0) at age 70 years. No germline RET germline variants nor other variants were found to explain this MTC variability. Conclusions: We could not confirm the previously reported finding of a somatic RET variant as likely responsible for the early onset and aggressiveness of MTC in a RET germline mutation carrier. Also, we found no RET germline variants that could explain the MTC variability among our index patients. We did, however, identify a somatic FLT3 R387Q variant with an unknown potential as genetic modifier. Further large-scale studies are needed to investigate genetic modifiers in RET L790F carriers.
KW - FLT3 R387Q
KW - gene variants
KW - L790F
KW - medullary thyroid carcinoma
KW - multiple endocrine neoplasia type 2
KW - REarranged during Transfection
KW - variability
UR - http://www.scopus.com/inward/record.url?scp=85084453659&partnerID=8YFLogxK
U2 - 10.3389/fendo.2020.00251
DO - 10.3389/fendo.2020.00251
M3 - Journal article
AN - SCOPUS:85084453659
SN - 1664-2392
VL - 11
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
M1 - 251
ER -