For the first time an oncogenic somatic mutation at amino acid 918 in the RET (rearranged during transfection) protein has been identified in small cell lung cancer (SCLC) tumors and enforced expression of this mutation within SCLC cell lines produced increased intracellular signaling and cell growth.
SCLC is a highly malignant form of lung cancer representing 15% of all lung cancers and is strongly associated with tobacco smoking.
NSCLC, representing 85% of lung cancer, has been extensively examined for genomic alterations and targeted therapies are approved for patients with certain mutations, however SCLC has not been examined with the same rigor and there are no approved targeted therapies for SCLC.
Investigators at Case Western University examined 6 SCLC tumors, 3 each from primary and metastatic tumors, for 238 somatic mutations across 19 oncogenes. RET wild type and mutant protein was then overexpressed in SCLC cell lines and these cell lines were examined for cell signaling, cell growth and responsiveness to two tyrosine kinase inhibitors of RET.
Results reported in the September issue of the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer (IASLC), revealed the RET M918T mutation in a metastatic SCLC tumor and that overexpression of this mutant protein in SCLC cell lines resulted in increased ERK signaling, MYC expression and increased cell proliferation.
Likewise, these cell lines overexpressing the RET protein became sensitive to ponatinib and vandetanib, tyrosine kinase inhibitors of RET. Decreased cell growth was the result of this inhibition of RET.
The authors say 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 authors caution that “the role of oncogenic RET mutations cannot be judged fairly until a larger number of tumors are genomically analyzed, including metastatic tumors”.
Co-author Dr. Shahab Babakoohi is a member of IASLC.
About the IASLC:
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated to the study of lung cancer. Founded in 1974, the association’s membership includes more than 4,000 lung cancer specialists in 80 countries. To learn more about IASLC please visit www.iaslc.org
Murry W. Wynes, PhD
IASLC Special Projects Manager
Rob Mansheim | Eurek Alert!
Nonstop Tranport of Cargo in Nanomachines
20.11.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik
Researchers find social cultures in chimpanzees
20.11.2018 | Universität Leipzig
Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.
Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
20.11.2018 | Life Sciences
20.11.2018 | Life Sciences
20.11.2018 | Physics and Astronomy