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Test ID: FROS1    
Lung Cancer, ROS1 (6q22) Rearrangement, FISH, Tissue

Useful For Suggests clinical disorders or settings where the test may be helpful

Identifying ROS1 gene rearrangements in patients with late-stage, lung adenocarcinomas that are negative for EGFR mutations and ALK rearrangements

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Lung cancer is the leading cause of cancer mortality in developed countries. The discovery of a variety of genetic alterations in non-small-cell lung cancer (NSCLC) has enabled the use of targeted therapy such as the anaplastic lymphoma kinase (ALK) inhibitor, crizotinib, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib, for NSCLC with ALK rearrangements and EGFR mutations, respectively.

 

The c-ros oncogene 1 (ROS1), originally described in glioblastomas, has been identified as a potential relevant therapeutic target in lung adenocarcinoma. Crizotinib has shown in vitro activity and early evidence of clinical activity in ROS1-rearranged tumors.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal cutoff for the probe set.

 

A positive result suggests rearrangement of the ROS1 locus and a tumor that may be responsive to ALK-inhibitor therapy. A negative result suggests no rearrangement of the ROS1 gene region at 6q22.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is not approved by the FDA, and it is best used as an adjunct to existing clinical and pathologic information.

 

Fixatives other than formalin (eg, Prefer, Bouin) may not be successful for FISH assays. Although FISH testing will not be rejected due to nonformalin fixation, results may be compromised.

 

Paraffin-embedded tissues that have been decalcified are generally unsuccessful for FISH analysis. The pathologist reviewing the hematoxylin and eosin-stained slide may find it necessary to cancel testing.

Supportive Data

The probe set was independently validated in a blinded study on 20 paraffin-embedded lung adenocarcinoma tissue samples and 25 noncancerous control samples. Rearrangements of ROS1 were verified in samples previously identified with a ROS1 rearrangement using reverse-transcriptase-PCR testing methods. The normal controls were used to generate a normal cut-off for this assay.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Suehara Y, Arcila M, Wang L, et al: Identification of KIF5B-RET and GOPC-ROS1 fusions in lung adenocarcinomas through a comprehensive mRNA-based screen for tyrosine kinase fusions. Clin Cancer Res 2012;18(24):6599-6608

2. Takeuchi K, Soda M, Togashi Y, et al: RET, ROS1 and ALK fusions in lung cancer. Nat Med 2012;18(3):378-381

3. Bergethon K, Shaw AT, Ou SH, et al: ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol 2012;30(8):863-870

4. Chin LP, Soo RA, Soong R, Ou SH: Targeting ROS1 with anaplastic lymphoma kinase inhibitors: a promising therapeutic strategy for a newly defined molecular subset of non-small-cell lung cancer. J Thorac Oncol 2012;7(11):1625-1630