Lung Cancer, RET (10q11) Rearrangement, FISH, Tissue
Identifying RET 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.
Abnormalities of the RET protooncogene at chromosome 10q11 have been identified as the causative genetic abnormality in the neoplasia predisposition syndrome multiple endocrine neoplasia type II (MEN2), as well as in thyroid carcinomas. Recently, chromosomal rearrangements of RET have been identified in a subset of lung adenocarcinomas. Patients with tumors harboring RET rearrangements may benefit from RET kinase inhibitors, but the clinical benefits of the inhibitor has not yet been clarified.
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.
A positive result is detected when the percent of cells with an abnormality exceeds the normal cut-off for the probe set.
A positive result suggests rearrangement of the RET locus and a tumor that may be responsive to RET kinase inhibitor therapy. A negative result suggests no rearrangement of the RET gene region at 10q11.
Clinical and pathological correlation is recommended.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is only for primary or metastatic lung tumors.
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.
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 RET were verified in samples previously identified with a RET 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. Matsubara D, Kanai Y, Ishikawa S, et al: Identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line, LD-2/ad. J Thorac Oncol 2012;7(12):1872-1876
3. Kohno T, Ichikawa H, Totoki Y, et al: KIF5B-RET fusions in lung adenocarcinoma. Nat Med 2012;18(3):375-377
4. Lipson D, Capelleti M, Yelensky R, et al: Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med 2012;18(3):382-384