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Updated: May 14, 2026
A Blood-based Test for the Detection of ROS1 and RET Fusion Transcripts from Circulating Ribonucleic Acid Using Digital Polymerase Chain Reaction
Published on: April 5, 2018
Identification of ROS1 rearrangement in gastric adenocarcinoma
Jeeyun Lee1, Seung Eun Lee, So Young Kang
1Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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.
Insights
A novel SLC34A2-ROS1 rearrangement was found in gastric cancer (GC). This discovery supports further investigation into ROS1 inhibitors for treating this specific molecular subtype of GC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chromosomal rearrangements of receptor tyrosine kinases (RTKs) are implicated in epithelial cancers.
- ROS1 rearrangements are known drivers in nonsmall cell lung cancer (NSCLC), responding to crizotinib.
- Gastric cancer (GC) currently lacks novel molecular targets beyond HER2-targeted therapy.
Purpose of the Study:
- To identify novel molecular targets in gastric cancer (GC).
- To investigate the role of ROS1 rearrangements in GC.
- To explore potential therapeutic strategies for GC based on identified molecular alterations.
Main Methods:
- Screening of 495 GC samples using ROS1 immunohistochemistry (IHC).
- ROS1 break-apart fluorescence in situ hybridization (FISH) and reverse transcriptase-polymerase chain reaction (RT-PCR) on IHC-positive samples.
- Assessment of HER2 amplification and MET expression in all samples.
Main Results:
- ROS1 rearrangements, specifically SLC34A2-ROS1 fusion transcripts, were identified in a subset of GC patients.
- Patients with SLC34A2-ROS1 fusions exhibited aggressive disease characteristics, including recurrence and early mortality.
- ROS1 IHC positivity did not independently predict overall survival.
Conclusions:
- An SLC34A2-ROS1 rearrangement represents a novel molecular alteration in gastric cancer (GC).
- These findings provide a strong rationale for evaluating ROS1 inhibitors in GC patients with this specific rearrangement.
- Targeting ROS1 may offer a new therapeutic avenue for a distinct molecular subset of GC.
