Format

Send to

Choose Destination
See comment in PubMed Commons below
J Thorac Oncol. 2014 Jan;9(1):118-20. doi: 10.1097/JTO.0000000000000015.

RET rearrangements in lung adenocarcinoma and radiation.

Author information

1
Departments of *Pathology, †Pharmacology, University of Pittsburgh; and 3University of Pittsburgh Cancer Institute, University of Pittsburgh, School of Medicine/Hematology-Oncology, Pittsburgh, Pennsylvania.

Abstract

BACKGROUND:

RET rearrangement, a hallmark of radiation-induced thyroid cancer, has been reported to occur in 1% of lung adenocarcinoma patients. Patients with this rearrangement tend to be younger and never smokers, raising a possibility of other causes, such as radiation. We hypothesized that RET chromosomal rearrangement may represent a genetic mechanism of radiation-induced lung cancer.

METHODS:

Two hundred forty-five consecutive primary lung adenocarcinomas without history of radiation and 38 lung adenocarcinoma patients with a history of therapeutic radiation for breast carcinoma or mediastinal Hodkgin lymphoma were tested for RET rearrangement by fluorescence in situ hybridization. Human lung adenocarcinoma cells (201T) were subjected to γ radiation and tested for RET gene fusions by reverse transcriptase-polymerase chain reaction and Southern blot hybridization.

RESULTS:

We identified one case with RET rearrangement in the group without history of radiation (1 of 240; 0.4%) and two cases in the group with history of radiation (2 of 37; 5.4%; P=0.0436). Both these patients were women, who were former smokers with a history of breast carcinoma treated with surgery and radiation. Furthermore, we found that RET fusions could be directly induced in 201T human lung cells by exposure to 1 Gy of γ radiation. All fusions identified were between RET and KIF5B genes, and no RET fusions to CCDC6 or NCOA4 genes, characteristic for thyroid cancer, were identified in the irradiated lung cells.

CONCLUSION:

RET fusions may represent a genetic mechanism of radiation-induced lung adenocarcinoma.

PMID:
24346100
PMCID:
PMC4836180
DOI:
10.1097/JTO.0000000000000015
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center