Trisomy 1q generating translocations in Wilms tumor

Area of Science:

• Cytogenetics
• Pediatric Oncology
• Cancer Genetics

Background:

• Unbalanced translocations leading to 1q trisomy are frequently observed in Wilms tumor (WT).
• These chromosomal abnormalities play a significant role in the development and progression of various cancers.

Purpose of the Study:

• To analyze eight unbalanced 1q translocations in WT cases and review existing literature.
• To identify common translocation partners and breakpoints associated with 1q trisomy in WT.
• To differentiate the roles of various translocations in tumor initiation versus progression.

Main Methods:

• Karyotyping of seven WT tumors.
• Review of published literature on 1q translocations in WT.
• Fluorescence in situ hybridization (FISH) using probes for 1q12 and 1q21.

Main Results:

• The der(16)t(1q;16q) translocation was identified in four tumors and is the most prevalent +1q generating translocation in WT, often acting as a primary abnormality.
• Four additional translocations involving chromosomes 9, 17, and 21 were identified, with 17p and 21p translocations occurring independently.
• The 17p and 21p translocations were secondary events, suggesting a role in tumor progression.
• FISH analysis confirmed variable breakpoints on 1q, predominantly at or centromeric to 1q12.

Conclusions:

• The der(16)t(1q;16q) translocation is a key event in Wilms tumor pathogenesis.
• Other 1q translocations, particularly those involving 17p and 21p, are secondary events implicated in tumor progression.
• Breakpoint heterogeneity on chromosome 1q exists, with a common region near 1q12.