Small Cell Lung Cancer Features Novel Oncogenic RET Mutation, According To New Research

Small Cell Lung Cancer Features Novel Oncogenic RET Mutation, According To New Research

RET Mutation in small cell lung cancerA team of scientists from Case Western University recently discovered a somatic mutation on oncogene RET in small cell lung cancer (SCLC) tumors that is responsible for tumor growth via activation of ERK and MYC signaling pathways.

The findings were published in September issue of Journal of Thoracic Oncology. The study is entitled “RET Mutations in Neuroendocrine Tumors: Including Small-Cell Lung Cancer.”

The authors analyzed six tumors from six different patients with SCLC, with three primary tumors and three others with metastatic tumors from the brain, pancreas, and adrenal gland. The tumor DNA was extracted and analyzed for 238 somatic mutations across 19 common oncogenes. The authors identified, by SEQUENOM analysis, two mutations — an RET M918T mutation in a brain metastasis and R970C mutation in a primary tumor. The team selected the M918T mutation for further analysis because of its association with a syndrome of medullary thyroid cancer (MTC). Using SCLC cell lines, the authors performed over expression studies with both RET wild-type and mutant protein leading to an increase in ERK and MYC signaling. Both pathways are involved in cell growth and proliferation, a hallmark of cancer.

Moreover, the author showed that with RET being a member of the receptor tyrosine kinase (RTK) superfamily, these cells were susceptible to tyrosine kinase inhibitors. Treatment with ponatinib and vandetanib, tyrosine kinase inhibitors of RET, resulted in decreased cell growth.

The authors commented that their work, “suggests that RET mutations play a potential role in some cases of SCLC as no other activating mutations were identified among the 19 oncogenes assayed in the tumor harboring the RET M918T mutation, potentially making M918T the driver mutation in this tumor. However, the “role of oncogenic RET mutations cannot be judged fairly until a larger number of tumors are genomically analyzed, including metastatic tumors.”

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