SYNE1 Mutation Is Associated with Increased Tumor Mutation Burden and Immune Cell Infiltration in Ovarian Cancer

Laura M Harbin; Nan Lin; Frederick R Ueland; Jill M Kolesar

doi:10.3390/ijms241814212

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SYNE1 Mutation Is Associated with Increased Tumor Mutation Burden and Immune Cell Infiltration in Ovarian Cancer

Journal article

Open access

Peer reviewed

SYNE1 Mutation Is Associated with Increased Tumor Mutation Burden and Immune Cell Infiltration in Ovarian Cancer

Laura M Harbin, Nan Lin, Frederick R Ueland and Jill M Kolesar

International journal of molecular sciences, Vol.24(18), 14212

09/18/2023

DOI: 10.3390/ijms241814212

PMCID: PMC10531966

PMID: 37762518

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https://doi.org/10.3390/ijms241814212View

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Abstract

SYNE1, a nuclear envelope protein critical for cellular structure and signaling, is downregulated in numerous malignancies. SYNE1 alterations are found in 10% of gynecologic malignancies and 5% of epithelial ovarian cancers. Previous studies demonstrated an association between SYNE1 mutation, increased tumor mutation burden (TMB), and immunotherapy response. This study evaluates the SYNE1 mutation frequency, association with TMB, and downstream effects of SYNE1 mutation in ovarian cancer. Genetic information, including whole-exome sequencing, RNA analysis, and somatic tumor testing, was obtained for consenting ovarian cancer patients at an academic medical center. Mutation frequencies were compared between the institutional cohort and The Cancer Genome Atlas (TCGA). Bioinformatics analyses were performed. In our cohort of 50 patients, 16 had a SYNE1 mutation, and 15 had recurrent disease. Median TMB for SYNE1 mutated patients was 25 compared to 7 for SYNE1 wild-type patients (p < 0.0001). Compared to the TCGA cohort, our cohort had higher SYNE1 mutation rates (32% vs. 6%, p < 0.001). Gene expression related to immune cell trafficking, inflammatory response, and immune response (z > 2.0) was significantly increased in SYNE1 mutated patients. SYNE1 mutation is associated with increased TMB and immune cell infiltration in ovarian cancer and may serve as an additional biomarker for immunotherapy response.

Mutation

Carcinoma, Ovarian Epithelial

Cytoskeletal Proteins - genetics

Female

Genital Neoplasms, Female

Humans

Mutation Rate

Nerve Tissue Proteins - genetics

Ovarian Neoplasms - genetics

Details

Title: Subtitle: SYNE1 Mutation Is Associated with Increased Tumor Mutation Burden and Immune Cell Infiltration in Ovarian Cancer
Creators: Laura M Harbin - University of Kentucky
Nan Lin - University of Kentucky
Frederick R Ueland - University of Kentucky
Jill M Kolesar - University of Kentucky
Resource Type: Journal article
Publication Details: International journal of molecular sciences, Vol.24(18), 14212
DOI: 10.3390/ijms241814212
PMID: 37762518
PMCID: PMC10531966
ISSN: 1661-6596
eISSN: 1422-0067
Grant note: P30 CA177558 / NCI NIH HHS
Language: English
Date published: 09/18/2023
Academic Unit: Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984696550902771

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