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Updated: Feb 28, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Genetic and epigenetic alterations affecting PARK-2 expression in cervical neoplasm among North Indian patients
Afreen Naseem1, Zafar Iqbal Bhat1, Ponnusamy Kalaiarasan2
11 Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, India.
Abstract:
The recent investigation on PARK-2, a putative tumor suppressor gene, has found that it has been altered in multiple human malignancies. However, the clinical impact of PARK-2 alteration in uterine cervix carcinoma has not yet been studied. Therefore, we aimed to examine mutations, promoter hypermethylation, and protein expression of PARK-2 among the North Indian patients and their association with clinical parameters to evaluate the implication of PARK-2 in the genesis of cervical cancer. A total of 168 patient samples were processed for mutational analysis by single-strand conformation polymorphism, sequencing, and further in silico analysis of the identified mutations. Promoter hypermethylation by methylation-specific polymerase chain reaction and expression of PARK-2 were performed using immunohistochemistry. Statistical correlation between molecular findings and the clinicopathological parameters was taken to figure out the meaningful outcome. As per our findings, 3.5% (6/168) tumors showed novel missense mutations in exon 11 of PARK-2. In silico analysis showed high structural deviations manifested by mutations, A398D and Y391N, in both mutant proteins as compared to wild type. Promoter hypermethylation was observed in total of 29% of (48/168) tumor samples. Furthermore, 46.43% tumors (78/168) exhibited loss of PARK-2 expression in cervical carcinoma. The loss of expression of PARK-2 when correlated with clinical parameters resulted in significant association with tumor stage (p = 0.002) and with histological grade (p = 0.025). However, only clinical stage remained significant after Bonferroni correction (p < 0.007). A trend was observed between PARK-2 promoter hypermethylation and its protein expression. Our study provided sufficient information and insight for investigation of PARK-2 and highlighted its role as a tumor suppressor gene in cervical cancer in North Indian population.
Insights
PARK-2 alterations, including mutations and hypermethylation, are linked to cervical cancer development in North India. Loss of PARK-2 expression significantly correlates with advanced tumor stage and grade, underscoring its tumor suppressor role.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- PARK-2 is a known tumor suppressor gene implicated in various human cancers.
- The role of PARK-2 in cervical cancer, particularly in the North Indian population, remains understudied.
- Understanding PARK-2's alterations is crucial for evaluating its implication in cervical cancer genesis.
Purpose of the Study:
- To investigate mutations, promoter hypermethylation, and protein expression of PARK-2 in North Indian cervical cancer patients.
- To analyze the association between PARK-2 alterations and clinical parameters in cervical cancer.
- To elucidate the tumor suppressor function of PARK-2 in cervical carcinogenesis.
Main Methods:
- Analysis of 168 cervical cancer patient samples.
- Mutational analysis using single-strand conformation polymorphism (SSCP) and sequencing.
- In silico analysis of identified mutations.
- Detection of promoter hypermethylation via methylation-specific PCR.
- Assessment of PARK-2 protein expression using immunohistochemistry.
- Statistical correlation with clinicopathological parameters.
Main Results:
- Novel missense mutations (A398D, Y391N) were identified in 3.5% of tumors, showing significant structural deviations.
- Promoter hypermethylation was observed in 29% of samples.
- Loss of PARK-2 protein expression occurred in 46.43% of tumors.
- Loss of PARK-2 expression significantly correlated with tumor stage (p=0.002) and histological grade (p=0.025), with stage remaining significant after correction (p<0.007).
- A trend was noted between promoter hypermethylation and reduced protein expression.
Conclusions:
- PARK-2 alterations, including mutations and epigenetic silencing via hypermethylation, play a role in cervical cancer development.
- Reduced PARK-2 expression is significantly associated with advanced clinical stage in cervical cancer.
- PARK-2 functions as a tumor suppressor gene in the North Indian cervical cancer population, warranting further investigation.
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