PMID- 33708852 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220421 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 9 IP - 3 DP - 2021 Feb TI - 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. PG - 225 LID - 10.21037/atm-20-4081 [doi] LID - 225 AB - 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. CI - 2021 Annals of Translational Medicine. All rights reserved. FAU - Jorgensen, Jan Trost AU - Jorgensen JT AD - Companion Diagnostics, Dx-Rx Institute, Fredensborg, Denmark. FAU - Mollerup, Jens AU - Mollerup J AD - Pathology Division, Agilent Technologies, Glostrup, Denmark. FAU - Yang, Hui AU - Yang H AD - Medical Sciences, Amgen Inc., Thousand Oaks, USA. FAU - Go, Ning AU - Go N AD - Medical Sciences, Amgen Inc., Thousand Oaks, USA. FAU - Nielsen, Karsten Bork AU - Nielsen KB AD - Bork Enterprises, Virum, Denmark. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC7940901 OTO - NOTNLM OT - Mesenchymal epithelial transition factor gene (MET) OT - amplification OT - deletion OT - fluorescence in situ hybridization (FISH) OT - gastric cancer COIS- 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. EDAT- 2021/03/13 06:00 MHDA- 2021/03/13 06:01 PMCR- 2021/02/01 CRDT- 2021/03/12 07:20 PHST- 2021/03/12 07:20 [entrez] PHST- 2021/03/13 06:00 [pubmed] PHST- 2021/03/13 06:01 [medline] PHST- 2021/02/01 00:00 [pmc-release] AID - atm-09-03-225 [pii] AID - 10.21037/atm-20-4081 [doi] PST - ppublish SO - Ann Transl Med. 2021 Feb;9(3):225. doi: 10.21037/atm-20-4081.