Variability in Medullary Thyroid Carcinoma in RET L790F Carriers: A Case Comparison Study of Index Patients

Jes Sloth Mathiesen*, Søren Grønlund Nielsen, Åse Krogh Rasmussen, Katalin Kiss, Karin Wadt, Anne Pernille Hermann, Morten Frost Nielsen, Stine Rosenkilde Larsen, Klaus Brusgaard, Anja Lisbeth Frederiksen, Christian Godballe, Maria Rossing

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

14 Downloads (Pure)

Abstrakt

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.

OriginalsprogEngelsk
Artikelnummer251
TidsskriftFrontiers in Endocrinology
Vol/bind11
Antal sider7
ISSN1664-2392
DOI
StatusUdgivet - 28. apr. 2020

Fingeraftryk

Dyk ned i forskningsemnerne om 'Variability in Medullary Thyroid Carcinoma in RET L790F Carriers: A Case Comparison Study of Index Patients'. Sammen danner de et unikt fingeraftryk.

Citationsformater