Mutational Analysis of BRAF, RAS, and EGFR Genes in Human Adrenocortical Carcinomas

Strategic Insights -

Research findings suggest that mutations in the BRAF, RAS, and EGFR genes may play a significant role in the development of human adrenocortical carcinomas. According to a new report published in the journal Endocrine-related Cancer, the serine/threonine kinase B-Raf and the epidermal growth factor receptor (EGFR) are key players in the Ras/Raf/MEK/ERK pathway, which relays extracellular signals for cell proliferation and survival. The study evaluated the presence of mutations in these genes in 35 tumor specimens and two cell lines, and found that BRAF mutations were present in 5.7% of carcinomas, while EGFR TK domain mutations were found in 11.4% of carcinomas.

Key Takeaways:

  • The study found that BRAF, RAS, and EGFR mutations occur in a subset of human adrenocortical carcinomas, with BRAF mutations present in 5.7% of carcinomas and EGFR TK domain mutations present in 11.4% of carcinomas.
  • The researchers concluded that inhibitors of the Ras/Raf/MEK/ERK and EGFR pathways represent candidate targeted therapies for future clinical trials in carefully selected patients with adrenocortical carcinomas harboring respective activating mutations.
  • The study found that adrenocortical carcinomas with BRAF and EGFR mutations exhibited stronger immunostaining for the phosphorylated forms of the MEK and ERK kinases than their wild-type counterparts.
  • The researchers note that EGFR-mutant carcinomas exhibited increased phosphorylation of EGFR (Tyr 992) compared with wild-type carcinomas.

Statistics:

  • 5.7% of adrenocortical carcinomas carried activating BRAF mutations.
  • 11.4% of adrenocortical carcinomas carried EGFR TK domain mutations.
  • 1 in 17 adrenocortical carcinomas carried a KRAS mutation.
  • 1 in 2 adrenocortical carcinomas carried NRAS mutations.
  • Adrenocortical carcinomas with BRAF and EGFR mutations exhibited increased phosphorylation of MEK and ERK kinases.

Sources:

  • Kotoula, V., et al. (2009). Mutational analysis of the BRAF, RAS and EGFR genes in human adrenocortical carcinomas. Endocrine-related Cancer, 16(2), 565-72.
  • Aristotle University of Thessaloniki, Dept. of Pathology, School of Medicine, University Campus, Thessaloniki 54006, Greece.