Genetic Alterations in Anaplastic Thyroid Carcinoma.

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Anaplastic thyroid cancer (ATC) is a rare but highly fatal malignancy, accounting for most thyroid cancer deaths.
• ATC can arise de novo or transform from differentiated thyroid cancer (DTC), with genetic mutations playing a key role.
• The MAP kinase and PI3K/AKT pathways are frequently implicated in ATC pathogenesis.

Purpose of the Study:

• To investigate the frequency of genetic alterations in the MAP kinase and PI3K/AKT pathways in patients with ATC.
• To identify potential genetic markers associated with ATC development and progression.

Main Methods:

• Retrospective analysis of 34 ATC patients' clinico-pathological data and FFPE tissues.
• Genetic analysis including BRAF V600E mutation screening (RFLP PCR, sequencing), RAS, PI3CA, p53 mutation analysis (sequencing), and RET/PTC translocation screening (Real Time PCR).

Main Results:

• BRAF V600E mutations were found in 29.4% of ATC patients, with a higher prevalence in those with a history of goiter and DTC.
• Patients with BRAF V600E mutations had a shorter mean survival (3.5 months) compared to BRAF-negative cases (5.5 months).
• p53 mutations were observed in 7 patients, and RAS mutations in 5.8%; no RET-PTC or PI3CA mutations were detected.

Conclusions:

• BRAF V600E and p53 mutations are the most common genetic alterations in the studied ATC cohort.
• The increased frequency of BRAF V600E in patients with prior goiter or DTC suggests a role in the neoplastic transformation of differentiated to anaplastic thyroid cancer.