Identification of ROS1 rearrangement in gastric adenocarcinoma. Issue 9 (7th February 2013)

• Record Type: Journal Article
• Authors: Lee, Jeeyun; Lee, Seung Eun; Kang, So Young; Do, In‐Gu; Lee, Sujin; Ha, Sang Yun; Cho, Jeonghee; Kang, Won Ki; Jang, Jiryeon; Ou, Sai‐Hong Ignatius; Kim, Kyoung‐Mee
• Is Part Of: Cancer. Volume 119:Issue 9(2013)
• Page Start: 1627
• Page End: 1635
• Publication Date: 2013-02-07
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.27967
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="abs1-1" sec-type="section"> <title>BACKGROUND:</title> <p>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 <italic>ROS1</italic>‐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.</p> </sec> <sec id="abs1-2" sec-type="section"> <title>METHODS:</title> <p>Anti‐ROS1 immunohistochemistry (IHC) was used to screen 495 GC samples and was followed by simultaneous <italic>ROS1</italic> break‐apart fluorescence in situ hybridization (FISH) and reverse transcriptase‐polymerase chain reaction (RT‐PCR) analyses in IHC‐positive samples. Fusion partners in <italic>ROS1</italic>‐rearranged GC were determined by RT‐PCR. In all 495 samples, <italic>HER2</italic> amplification was identified with FISH, and MET expression was identified by IHC.</p> </sec> <sec id="abs1-3" sec-type="section"> <title>RESULTS:</title> <p>Twenty‐three tumor samples were ROS1 IHC‐positive. Three of 23 patients were <italic>ROS1</italic> FISH positive, <italic>HER2</italic> FISH negative, and negative for MET overexpression; and 2 of those 3 patients harbored a solute carrier family 34 (sodium phosphate), member 2 (<italic>SLC34A2)</italic>‐<italic>ROS1</italic> fusion transcripts. No fusion partner was identified in the third patient. Both patients who had <italic>SLC34A2</italic>‐<italic>ROS1</italic> 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.</p> </sec> <sec id="abs1-4" sec-type="section"> <title>CONCLUSIONS:</title> <p>In this study, an <italic>SLC34A2</italic>‐<italic>ROS1</italic> 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. Cancer 2013. © 2013 American Cancer Society.</p> </sec> </abstract>