Deleted in lung and esophageal cancer 1

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Overview

Deleted in Lung and Esophageal Cancer 1 (DLEC1) is a tumor suppressor gene located on chromosome 3p22.3. It is implicated in the pathogenesis of lung cancer and esophageal cancer. The gene is often found to be deleted or downregulated in these cancers, suggesting its role in tumor suppression.

Genomic Location and Structure

DLEC1 is located on the short arm of chromosome 3, specifically at the 3p22.3 locus. The gene spans approximately 630 kilobases and consists of 37 exons. The protein encoded by DLEC1 is a large protein with multiple domains, which are thought to be involved in its tumor suppressor functions.

Function

The exact function of DLEC1 is not fully understood, but it is believed to play a role in regulating cell growth and apoptosis. Studies suggest that DLEC1 may interact with other proteins involved in cell cycle regulation and DNA repair. Its loss or downregulation can lead to uncontrolled cell proliferation, a hallmark of cancer.

Role in Cancer

DLEC1 is frequently deleted or epigenetically silenced in non-small cell lung cancer (NSCLC) and esophageal squamous cell carcinoma (ESCC). The loss of DLEC1 expression is associated with poor prognosis and advanced disease stage in these cancers.

Lung Cancer

In lung cancer, particularly NSCLC, DLEC1 is often found to be deleted or methylated, leading to its inactivation. Restoration of DLEC1 expression in lung cancer cell lines has been shown to inhibit cell growth and induce apoptosis, supporting its role as a tumor suppressor.

Esophageal Cancer

In esophageal cancer, DLEC1 is similarly inactivated through deletion or promoter hypermethylation. The re-expression of DLEC1 in esophageal cancer cells can suppress tumor growth, indicating its potential as a therapeutic target.

Clinical Implications

The frequent inactivation of DLEC1 in lung and esophageal cancers makes it a potential biomarker for diagnosis and prognosis. Additionally, therapies aimed at restoring DLEC1 function or expression could be beneficial in treating these cancers.

Research Directions

Ongoing research is focused on understanding the molecular mechanisms by which DLEC1 exerts its tumor suppressor effects. Studies are also exploring the potential of DLEC1 as a target for epigenetic therapy, aiming to reverse its silencing in cancer cells.

Conclusion

DLEC1 is a critical tumor suppressor gene involved in the pathogenesis of lung and esophageal cancers. Its frequent deletion or silencing in these cancers highlights its importance in maintaining normal cellular functions and preventing tumor development.


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Contributors: Prab R. Tumpati, MD