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. 2020 Jun 29;12(7):1724.
doi: 10.3390/cancers12071724.

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

Binnari Kim  1   2   3 , So Young Kang  1 , Deokgeun Kim  4 , You Jeong Heo  5 , Kyoung-Mee Kim  1   2
Affiliations

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

Binnari Kim et al. Cancers (Basel). .

Abstract

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.

Keywords: PTEN; gastric cancer; inactivation; nonsense mutation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Representative cases of Phosphatase and Tensin Homolog (PTEN) immunohistochemistry and PTEN mutation confirmed by Integrative Genomics Viewer.
Figure 2
Figure 2
The distribution and prevalence of co-occurring genetic alterations associated with phosphatase and tensin homolog (PTEN), microsatellite instability (MSI) status, Epstein–Barr virus (EBV), HER2, and PD-L1.
See this image and copyright information in PMC

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