Abstract 1769
Background
Uveal melanoma is the most common primary cancer of the eye mainly arising from choroid which metastasizes to the liver and frequently leads to death. Till date, there is no current study on the correlation between ATM and BAP1 expression in uveal melanoma. Both proteins trigger DNA damage response (DDR) which leads to DNA repair. Literature reveals that ATM modifies the BAP1for the activation of DNA repair which signifies that there is a connecting link between ATM and BAP1. Therefore, the aim of the study is to detect the co-expression of ATM and BAP1 protein in uveal melanoma patients.
Methods
Sixty-nine formalin fixed paraffin embedded choroidal melanoma samples were taken to evaluate the expression of ATM and BAP1 by immunohistochemistry and validated by western blotting. To check BAP1 mutation, Sanger sequencing was done on control and UM samples. Results were then correlated with clinical and histopathological parameters. To determine the prognostic significance, Kaplan–Meier analysis and multivariate analysis by Cox’s Proportional Hazards Model was performed.
Results
There was a male preponderance in our study. Histopathological high-risk factors were identified in 48% cases. Both ATM and BAP1 show loss of nuclear expression in 55% of the cases and this was statistically significant with high pigmentation, LTD >10mm, TIL and cell type (p < 0.05). On multivariate analysis, advanced tumour staging and epithelioid cell type are found to be independent prognostic factors.
Conclusions
Our data suggest that loss of nATM and nBAP1might serve as a potential prognostic marker in the pathogenesis of uveal melanoma leading to increased risk of metastasis. These findings demonstrate the synergistic role of ATM and BAP1 proteins and may have a therapeutic potential in uveal melanoma. However, further studies are required in a larger cohort of patients with longer follow up and translational validation needs to be performed.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5011 - LCSCAF1 maintains cancer stem-like traits by stabilizing c-Myc protein and promotes metastasis and recurrence in lung cancer
Presenter: Tao Guo
Session: Poster Display session 1
Resources:
Abstract
4955 - XAF1 Enhances Temozolomide Induced Autophagic Cell Death through AMPK signaling pathway
Presenter: Mingoo Lee
Session: Poster Display session 1
Resources:
Abstract
5616 - The effect of cortisol on methylation patterns in breast cancer cell lines
Presenter: Haya Intabli
Session: Poster Display session 1
Resources:
Abstract
4649 - Global and sex-specific epigenome-wide association studies for the identification of the main methylated loci related to smoking in a Mediterranean population
Presenter: Judith Begona Ramirez Sabio
Session: Poster Display session 1
Resources:
Abstract
4984 - Whole transcriptomics analyses of mimicking Circulating Tumor Cells (CTCs) by single-cell RNA sequencing (scRNAseq)
Presenter: Jessica Garcia
Session: Poster Display session 1
Resources:
Abstract
5926 - Comparison of enzymatic- and bisulfite conversion to map the plasma cell-free methylome in cancer
Presenter: Nicole Lambert
Session: Poster Display session 1
Resources:
Abstract
5454 - Detection of low mutations in hepatocellular carcinoma by using circulating tumor DNA
Presenter: Esl Kim
Session: Poster Display session 1
Resources:
Abstract
4428 - Variants in the JAK1 and JAK2 genes in the risk and prognosis of patients with cutaneous melanoma
Presenter: Bruna Carvalho
Session: Poster Display session 1
Resources:
Abstract
4409 - P-Rex1 expression in breast cancer patients.
Presenter: Angela Lara Montero
Session: Poster Display session 1
Resources:
Abstract
4185 - Modulation of Risk of Cutaneous Melanoma Patients by Variants in STAT3 Gene and Functional Analysis
Presenter: Gabriela Gomez
Session: Poster Display session 1
Resources:
Abstract