Skip Navigation LinksHome > September 2014 - Volume 9 - Issue 9 > RET Mutation and Expression in Small-Cell Lung Cancer
Journal of Thoracic Oncology:
doi: 10.1097/JTO.0000000000000234
Original Articles

RET Mutation and Expression in Small-Cell Lung Cancer

Dabir, Snehal PhD*; Babakoohi, Shahab MD; Kluge, Amy BS*; Morrow, James J. BS‡§; Kresak, Adam BS§; Yang, Michael MD§; MacPherson, David PhD; Wildey, Gary PhD*; Dowlati, Afshin MD*

Collapse Box

Abstract

Background:

There is growing interest in defining the somatic mutations associated with small-cell lung cancer (SCLC). Unfortunately, a serious blockade to genomic analyses of this disease is a limited access to tumors because surgery is rarely performed. We used our clinical/pathologic database of SCLC patients to determine the availability of biopsy specimens that could be used for genomic studies and to identify tumors for initial oncogene analysis.

Methods:

DNA was extracted from six tumors, three primary and three metastatic, and analyzed by SEQUENOM platform technology.

Results:

Primary-resected tumor tissue represents less than 3% of all diagnostic specimens in this disease, highlighting the limited access to tissue sufficient for comprehensive genomic analyses. We identified an activating M918T RET somatic mutation in a metastatic SCLC tumor specimen. Bioinformatic search identified RET mutations in other SCLC studies. Stable overexpression of both mutant M918T and wild-type RET in two SCLC cell lines, H1048 and SW1271, activated ERK signaling, MYC expression, and increased cell proliferation, particularly by mutant RET. Stable cells became sensitized to the RET tyrosine kinase inhibitors, vandetanib and ponatinib. Further analysis of RET mRNA expression in SCLC revealed wide variability in both cells and tumors, and SCLC cells demonstrated significantly higher RET expression compared with adenocarcinoma lung cells.

Conclusions:

Our data suggest that a subpopulation of SCLC patients may derive benefit from tyrosine kinase inhibitors targeting RET. Coupled with the presence of RET fusion proteins in non-small-cell lung cancer, our data indicate an emerging role for RET in SCLC.

Copyright © 2014 by the International Association for the Study of Lung Cancer

Login

Article Tools

Share

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.

Other Ways to Connect

Twitter
twitter.com/JTOonline

 



Visit JTO.org on your smartphone. Scan this code (QR reader app required) with your phone and be taken directly to the site.

 For additional oncology content, visit LWW Oncology Journals on Facebook.