Terminal 18q deletions are stabilized by neotelomeres

Area of Science:

• Genetics
• Molecular Biology
• Genomics

Background:

• Human chromosomes possess protective tandem repeat (TTAGGG)n telomeres crucial for replication and integrity.
• Chromosomal breakage necessitates stabilization via telomere healing or telomere capture.
• Mechanisms of stabilization for 18q terminal deletions are sparsely reported.

Purpose of the Study:

• To investigate the molecular mechanisms stabilizing 18q terminal deletions.
• To determine if telomere healing or telomere capture is the predominant mechanism.

Main Methods:

• Analysis of nine patients with 18q terminal deletion using G-banding and genomic array.
• Fluorescence in situ hybridization (FISH) with PNA probes to detect telomeric signals.
• Fine-mapping of breakpoints using customized arrays and sequencing of deletion junctions.

Main Results:

• Telomeric signals were detected on all tested deleted chromosomes.
• Sequencing of six terminal deletion junctions revealed direct attachment of telomeric sequences to breakpoints.
• Minimal microhomology at breakpoints; no breaks in low copy repeat (LCR) regions.
• Repetitive elements were found near breakpoints in five patients.

Conclusions:

• All six sequenced deleted chromosomes were likely stabilized by telomere healing.
• Neotelomere formation is the probable mechanism for stabilizing 18q terminal deletions.