Homozygous Deletion

A homozygous deletion is the loss of both copies of a specific gene or DNA region, one inherited from each parent, in a cell. Because no working copy of the gene remains, the protein it normally produces is absent, which can drive cancer when the missing gene is a tumor suppressor. In mesothelioma, homozygous deletion of certain genes is one of the most common and characteristic genetic changes found in tumor tissue.

Origin

The term combines "homozygous" (from Greek homos, same, and zygotos, paired), meaning both copies of a gene match, with "deletion," referring to missing DNA. The concept became central to cancer genetics in the 1980s as researchers mapped tumor suppressor gene losses, and it gained diagnostic importance in mesothelioma after the discovery of frequent CDKN2A (p16) deletions in the 1990s.

Significance in Asbestos Context

Homozygous deletion of the CDKN2A gene (on chromosome 9p21) is found in roughly 70-80% of pleural mesotheliomas and is one of the most reliable molecular markers used to distinguish mesothelioma from benign reactive changes in the pleura, a distinction that can be very difficult under the microscope alone. Pathologists often test for this deletion using FISH (fluorescence in situ hybridization) when a biopsy is ambiguous, and a positive result strongly supports a malignant diagnosis. Deletions of other genes such as BAP1 and MTAP are also common in mesothelioma and may influence prognosis, eligibility for targeted therapy trials, and how the case is characterized in expert reports.

Example Sentence

The pathology report noted a homozygous deletion of CDKN2A by FISH testing, which confirmed the diagnosis of mesothelioma rather than benign pleural thickening.

Related Terms

CDKN2A, BAP1, MTAP, FISH (Fluorescence In Situ Hybridization), Tumor Suppressor Gene, Mesothelioma

Notes

• Ask your oncologist or pathologist whether FISH testing for CDKN2A (9p21) deletion was performed on your biopsy. It can be decisive when the diagnosis is uncertain.
• Request a copy of the full pathology and molecular testing report; the specific genes deleted (CDKN2A, BAP1, MTAP) may affect clinical trial eligibility and prognosis.
• If MTAP loss is reported, ask about emerging targeted therapies and trials directed at MTAP-deleted tumors (including PRMT5 inhibitors).
• Preserve all molecular pathology reports. They document the biological diagnosis and can be important evidence in a legal claim.