Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Methylthioadenosine phosphorylase (MTAP) is crucial for adenine salvage and methionine synthesis.
• The MTAP gene resides on chromosome 9p21, often co-deleted with tumor suppressors p15(INK4b) and p16(INK4a).
• Alterations in MTAP are frequently observed in various cancers.

Purpose of the Study:

• To determine the frequency of molecular alterations in the MTAP gene in osteosarcoma.
• To investigate the correlation between MTAP gene status and its expression at mRNA and protein levels.
• To explore potential therapeutic implications of MTAP loss in osteosarcoma.

Main Methods:

• Analysis of genomic DNA from 96 high-grade osteosarcoma patient samples and 3 cell lines using PCR for MTAP gene deletions.
• Quantification of MTAP RNA expression via semiquantitative reverse transcription-PCR.
• Assessment of MTAP protein levels using immunohistochemistry.

Main Results:

• MTAP gene deletions were detected in 37.5% (36/96) of osteosarcoma patient samples.
• Absence of detectable MTAP mRNA and protein correlated with observed gene deletions.
• MTAP deletions were also identified in sequential tumor samples from four patients.

Conclusions:

• The MTAP gene is frequently deleted in osteosarcoma, resulting in loss of MTAP expression.
• These findings suggest that targeting de novo purine synthesis or methionine depletion could be effective treatments for osteosarcoma patients with MTAP-deficient tumors.