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Cancer. 2013 May 1;119(9):1627-35. doi: 10.1002/cncr.27967. Epub 2013 Feb 7.

Identification of ROS1 rearrangement in gastric adenocarcinoma.

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1
Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Abstract

BACKGROUND:

Recently, chromosomal rearrangements involving receptor tyrosine kinases (RTKs) have been described in common epithelial malignancies, including nonsmall cell lung cancer (NSCLC), colorectal cancer, and breast cancer. One of these RTKs, c-ros oncogene 1, receptor tyrosine kinase (ROS1), has been identified as a driver mutation in NSCLC, because its inhibition by crizotinib, an anaplastic lymphoma receptor tyrosine kinase (ALK)/met proto-oncogene hepatocyte growth factor receptor (MET)/ROS1 inhibitor, led to significant tumor shrinkage in ROS1-rearranged NSCLC. Currently, only human epidermal growth factor 2 (HER2)-targeted therapy in combination with chemotherapy has been successful in significantly prolonging the survival of patients with advanced gastric cancer (GC). There is a need for the discovery of additional novel targets in GC.

METHODS:

Anti-ROS1 immunohistochemistry (IHC) was used to screen 495 GC samples and was followed by simultaneous ROS1 break-apart fluorescence in situ hybridization (FISH) and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses in IHC-positive samples. Fusion partners in ROS1-rearranged GC were determined by RT-PCR. In all 495 samples, HER2 amplification was identified with FISH, and MET expression was identified by IHC.

RESULTS:

Twenty-three tumor samples were ROS1 IHC-positive. Three of 23 patients were ROS1 FISH positive, HER2 FISH negative, and negative for MET overexpression; and 2 of those 3 patients harbored a solute carrier family 34 (sodium phosphate), member 2 (SLC34A2)-ROS1 fusion transcripts. No fusion partner was identified in the third patient. Both patients who had SLC34A2-ROS1 transcripts had poorly differentiated histology with recurrence and death within 2 years of curative surgery. ROS1 IHC-positive status was not identified as an independent prognostic factor for overall survival.

CONCLUSIONS:

In this study, an SLC34A2-ROS1 rearrangement was identified in GC, and the results provide a rationale for investigating the clinical efficacy of ROS1 inhibitors in this unique molecular subset of GC. Society.

PMID:
23400546
DOI:
10.1002/cncr.27967
[Indexed for MEDLINE]
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