The following is a summary of “BRAFV600E/pTERT double mutated papillary thyroid cancers exhibit immune gene suppression,” published in the December 2024 issue of Endocrinology by Chindris et al.  

The BRAFV600E mutation (BRAF^mut) is commonly found in papillary thyroid cancer (PTC), and most people with this mutation have a favorable outcome however when a TERT promoter mutation (pTERT^mut) occurs alongside BRAF^mut the results in more aggressive disease.  

Researchers conducted a retrospective study to explore the relationship between BRAF^mut, pTERT^mut, and immune gene dysregulation in people with PTC.  

They analyzed 770 immune gene transcripts using the NanoString nCounter^® PanCancer Immune Profiling Panel (P<0.05) in 147 PTC tumor samples.  

The results showed 40 immune transcripts were differentially expressed in BRAF^mut pTERT^mut vs. BRAF^mut pTERT wildtype (pTERT^wt) tumors (P<0.05). Transcripts related to lymphoid cells, antigen-presenting cells, and cytotoxic cells, including chemokines, cytokines, checkpoint proteins, interferon markers, TNF superfamily proteins, and BMP markers, were significantly repressed in BRAF^mut pTERT^mut samples. Deconvolution analysis confirmed an increased presence of M2 macrophages in BRAF^mut pTERT^mut tumors from the Mayo cohort, and a reduced abundance of M1 macrophages in BRAF^mut pTERT^mut tumors from The Cancer Genome Atlas (TCGA) cohort compared to BRAF^mut pTERT^wt tumors. Immune gene pathways were enriched in BRAF^mut pTERT^wt tumors in both the Mayo and TCGA cohorts, while BRAF^mut pTERT^mutshowed no such enrichment.  

They concluded that the pTERT^mut mutation may be linked to immune gene suppression in PTC, explaining its more aggressive behavior when combined with the BRAF^mut, mutation.  

Source: frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1440722/full