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Open AccessArticle

PTEN Protein Loss and Loss-of-Function Mutations in Gastric Cancers: The Relationship with Microsatellite Instability, EBV, HER2, and PD-L1 Expression

1
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
2
Center of Companion Diagnostics, Samsung Medical Center, Seoul 06351, Korea
3
Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea
4
Department of Clinical Genomics, Samsung Medical Center, Seoul 06351, Korea
5
The Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(7), 1724; https://doi.org/10.3390/cancers12071724
Received: 15 June 2020 / Accepted: 25 June 2020 / Published: 29 June 2020
Inactivation of phosphatase and tensin homolog (PTEN) is caused by multiple mechanisms, and loss of PTEN activity is related to the progression of various cancers. In gastric cancer (GC), the relationship between the loss of PTEN protein expression and various genetic alterations remains unclear. The effects of microsatellite instability (MSI), Epstein–Barr virus (EBV), HER2 overexpression, and PD-L1 expression on PTEN mutation have not been fully explored. We performed comprehensive cancer panel tests with a cohort of 322 tumor samples from patients with advanced GC. Immunohistochemistry for PTEN protein was performed in all cases, and the loss of protein expression was defined as a complete absence of nuclear staining. In total, 34 cases (10.6%) had pathogenic PTEN mutations, of which 19 (55.9%) showed PTEN protein loss. The most common PTEN variants associated with protein loss were p.R130 (n = 4) followed by p.R335, p.L265fs, and deletions (n = 2). All the ten nonsense mutations identified in the samples resulted in PTEN inactivation. In the remaining 288 GC cases with wild-type PTEN, protein loss was found in 35 cases (12.2%). Thus, PTEN mutations were significantly associated with PTEN protein loss (p = 5.232 × 10−10), high MSI (p = 3.936 × 10−8), and EBV-positivity (p = 0.0071). In conclusion, our results demonstrate that loss-of-function mutations in PTEN are a frequent genetic mechanism of PTEN inactivation in GC. View Full-Text
Keywords: PTEN; nonsense mutation; inactivation; gastric cancer PTEN; nonsense mutation; inactivation; gastric cancer
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Kim, B.; Kang, S.Y.; Kim, D.; Heo, Y.J.; Kim, K.-M. PTEN Protein Loss and Loss-of-Function Mutations in Gastric Cancers: The Relationship with Microsatellite Instability, EBV, HER2, and PD-L1 Expression. Cancers 2020, 12, 1724.

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