scholarly journals RAC1 Alterations Induce Acquired Dabrafenib Resistance in Association with Anaplastic Transformation in a Papillary Thyroid Cancer Patient

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4950
Author(s):  
Rozita Bagheri-Yarmand ◽  
Naifa L. Busaidy ◽  
Elena McBeath ◽  
Brian P. Danysh ◽  
Kurt W. Evans ◽  
...  

BRAF-activating mutations are the most frequent driver mutations in papillary thyroid cancer (PTC). Targeted inhibitors such as dabrafenib have been used in advanced BRAF-mutated PTC; however, acquired resistance to the drug is common and little is known about other effectors that may play integral roles in this resistance. In addition, the induction of PTC dedifferentiation into highly aggressive KRAS-driven anaplastic thyroid cancer (ATC) has been reported. We detected a novel RAC1 (P34R) mutation acquired during dabrafenib treatment in a progressive metastatic lesion with ATC phenotype. To identify a potential functional link between this novel mutation and tumor dedifferentiation, we developed a cell line derived from the metastatic lesion and compared its behavior to isogenic cell lines and primary tumor samples. Our data demonstrated that RAC1 mutations induce changes in cell morphology, reorganization of F-actin almost exclusively at the cell cortex, and changes in cell adhesion properties. We also established that RAC1 amplification, with or without mutation, is sufficient to drive cell proliferation and resistance to BRAF inhibition. Further, we identified polyploidy of chromosome 7, which harbors RAC1, in both the metastatic lesion and its derived cell line. Copy number amplification and overexpression of other genes located on this chromosome, such as TWIST1, EGFR, and MET were also detected, which might also lead to dabrafenib resistance. Our study suggests that polyploidy leading to increased expression of specific genes, particularly those located on chromosome 7, should be considered when analyzing aggressive thyroid tumor samples and in further treatments.

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Fevziye Burcu Sirin ◽  
Hakan Korkmaz

AbstractIn the present study we report a case of thyroglobulin (TGB) measurement interference in a total thyroidectomized and radio-ablated 61-year old woman with papillary thyroid cancer. We investigated possible interference in the measurement of TGB due to discordant TGB in relation to clinical condition during the follow-up period. Serum TGB was measured with the chemiluminescence method using Beckman Coulter Unicel DxI 800 instrument. To investigate possible interference in TGB measurement serial dilutions, polyethylene glycol precipitation (PEG), treatment with heterophile blocking tube (HBT), rheumatoid factor level determination and retesting of TGB with an alternative method were performed. Serial dilutions of the serum sample revealed linearity but a remarkable decrease in TGB in the patient’s serum samples post PEG and post HBT treatments. Also, TGB results under functional sensitivity level obtained with a different method suggested that TGB interference developed due to heterophile antibody presence in the serum sample. The patient had unnecessarily undergone expensive imaging techniques, and invasive procedures such as lymph node fine needle aspiration biopsy, before the analytical interference was suspected by the clinician. This report illustrates the importance of early communication and close collaboration between clinicians and laboratorians in order to avoid unnecessary clinical intervention.


2019 ◽  
Vol 10 (4) ◽  
pp. 3178-3181
Author(s):  
Punitha S ◽  
Vedha pal jeyamani ◽  
Sindhu S ◽  
Bhuvaneshwari P ◽  
Arshath A

Thyroid carcinoma is the majority widespread endocraine malignancy in that papillary thyroid cancer is a well-differentiated type. Since hyperthyroidism protects from thyroid cancer due to lack of reproduction of thyroid tissue by the thyroid-stimulating hormone. The papillary carcinoma is the fast-growing and metastases to local region rapidly. A 60 years old post menopausal women with a known case of hypertension of past 6 years on treatment and with hyperthyroidism of past 2 months was presented in the outpatient department in the hospital with chief complaints of mass in the neck with dyphagia, cough, breathlessness, sense of fullness and odynophagia of past 2 weeks. On physical and general examination patient found with diffuse thyroid swelling with enlarged right sided lymph node. The patient was diagnosed with papillary thyroid caricinoma with various investigation reports includes CT Scan, Immouno history chemistry reports, Histopathology and Two fine-needle aspiration biopsies. The patient has undergone 6 cycles of chemotherapy with the corticosteroids, anti-cancer drugs which includes Vincristine, Cyclophosphamide, Doxorubicin, anti- emetic drugs and also with H2 receptor blockers. The papillary thyroid cancer is common and occurs predominantly in females than in males and with good prognosis and decreased death rates. The higher level of thyroid function is very rare in case of PTC.


Author(s):  
Angelica Perna ◽  
Antonio De Luca ◽  
Laura Adelfi ◽  
Tammaro Pasquale ◽  
Bruno Varriale ◽  
...  

1996 ◽  
Vol 90 (1) ◽  
pp. 70-74 ◽  
Author(s):  
Marille E. Herrmann ◽  
Peter A. Lalley ◽  
Linea L. Rydstedt ◽  
Eckart Meese ◽  
Charles H. Lang ◽  
...  

2021 ◽  
Vol 46 (3) ◽  
Author(s):  
Chenguang Liu ◽  
Fangqin Yu ◽  
Runsheng Ma ◽  
Lele Zhang ◽  
Gongbo Du ◽  
...  

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