Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Feb;9(3):225.
doi: 10.21037/atm-20-4081.

MET deletion is a frequent event in gastric/gastroesophageal junction/esophageal cancer: a cross-sectional analysis of gene status and signal distribution in 1,580 patients

Jan Trøst Jørgensen  1 , Jens Mollerup  2 , Hui Yang  3 , Ning Go  3 , Karsten Bork Nielsen  4
Affiliations

MET deletion is a frequent event in gastric/gastroesophageal junction/esophageal cancer: a cross-sectional analysis of gene status and signal distribution in 1,580 patients

Jan Trøst Jørgensen et al. Ann Transl Med. 2021 Feb.

Abstract

Background: MET gene aberrations are found in several human cancers including gastric, ovarian and lung. In a large multinational cohort of patients with gastric/gastroesophageal junction/esophageal (G/GEJ/E) adenocarcinoma we assessed the MET status with respect to amplification and deletion and correlate the results with the phenotypical gene signal distribution pattern.

Methods: Tissue specimens from 1,580 patients were analyzed using a novel fluorescence in situ hybridization (FISH) assay employing a MET/CEN-7 IQFISH Probe Mix. MET amplification and deletions were defined as a MET/CEN-7 ratio ≥2.0 and a MET/CEN-7 ratio <0.8, respectively. Furthermore, the link between the MET gene status and the phenotypical signal distribution was investigated.

Results: The prevalence of MET amplification and deletions was found to be 7.2% and 8.7%, respectively. Significant differences were observed with regard to geographic regions and sex. The Asian population had the highest percentage of MET amplification (9.4%) and the lowest percentage of deletions (3.2%). MET deletions was found more frequently among males (10.1%) compared to females (5.3%) and in esophagus (17.6%) compared to the stomach (5.7%). More than 50% of the patients who harbored MET gene amplification had a heterogeneous distribution of the FISH signals. Patients with a focal signal distribution were solely to be found among the MET amplified population. MET deletion were mainly observed in the group of patients with a homogenous signal distribution.

Conclusions: The screening data from this cross-sectional study showed that MET deletion and amplification are frequent events in G/GEJ/E cancer, which are linked to different phenotypical signal distribution patterns. The role of MET deletion in relation to tumor development is not fully understood but it is likely to play a role in the oncogenic transformation of the cells.

Keywords: Mesenchymal epithelial transition factor gene (MET); amplification; deletion; fluorescence in situ hybridization (FISH); gastric cancer.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-4081). JTJ reports other from Employee of Agilent Technologies, personal fees from Agilent Technologies, during the conduct of the study; personal fees from Leo Pharma, personal fees from Alligator Bioscience, personal fees from Agilent Technologies, personal fees from Oncology Venture, personal fees from Azanta, personal fees from Euro Diagnostica, outside the submitted work. He also serves as an unpaid editorial board member of Annals of Translational Medicine from Nov 2016 to Oct 2022. JM reports personal fees from employment by Agilent Technologies, outside the submitted work. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Dot plot of MET/CEN-7 ratios versus the signal distribution pattern for all patient specimens (N=1,579) (A). Data on signal distribution is missing for one patient. Dot plot of MET/CEN-7 ratios versus the signal distribution pattern for all patient specimens up to a MET/CEN-7 ratio of 3.0 (N=1,499) (B). MET, mesenchymal epithelial transition factor gene; CEN-7, centromere of chromosome 7.
See this image and copyright information in PMC

References

    1. Cooper CS, Park M, Blair DG, et al. Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature 1984;311:29-33. 10.1038/311029a0 - DOI - PubMed
    1. Marano L, Chiari R, Fabozzi A, et al. c-Met targeting in advanced gastric cancer: An open challenge. Cancer Lett 2015;365:30-6. 10.1016/j.canlet.2015.05.028 - DOI - PubMed
    1. Matsumoto K, Umitsu M, De Silva DM, et al. Hepatocyte growth factor/MET in cancer progression and biomarker discovery. Cancer Sci 2017;108:296-307. 10.1111/cas.13156 - DOI - PMC - PubMed
    1. Bradley CA, Salto-Tellez M, Laurent-Puig P, et al. Targeting c-MET in gastrointestinal tumours: rationale, opportunities and challenges. Nat Rev Clin Oncol 2017;14:562-76. 10.1038/nrclinonc.2017.40 - DOI - PubMed
    1. Kawakami H, Okamoto I, Okamoto W, et al. Targeting MET Amplification as a New Oncogenic Driver. Cancers (Basel) 2014;6:1540-52. 10.3390/cancers6031540 - DOI - PMC - PubMed

LinkOut - more resources