Most Common Structural Chromosomal Abnormalities in MDS Patients
The most common structural chromosomal abnormalities in MDS patients are deletions (option C). According to the most recent guidelines from the American College of Medical Genetics and Genomics (ACMG), deletions are the predominant chromosomal abnormalities in myelodysplastic syndromes, with clonal copy number alterations (CNAs) being significantly more common than balanced structural abnormalities 1.
Evidence Supporting Deletions as Most Common
Specific Deletion Patterns
The most frequent deletions observed in MDS include:
- 5q deletions (del(5q)): Occurring in 10-15% of MDS patients 1
- 7q deletions (del(7q)): Occurring in approximately 10% of patients 1
- 20q deletions: Common enough to be included in standard MDS FISH panels 1
- 17p deletions: Associated with TP53 abnormalities 1
The ACMG technical standards specifically state that "in these myeloid neoplastic disorders, clonal CNAs and CN-LOH are the most common chromosomal abnormalities, whereas balanced structural abnormalities do not play a major role" 1.
Diagnostic Testing Recommendations
The European LeukemiaNet guidelines also support this conclusion by recommending FISH panels that primarily target deletion abnormalities:
- -5/5q- probes
- -7/7q- probes
- 20q deletion probes
- TP53 (17p13.1) deletion probes 1
Other Chromosomal Abnormalities in MDS
Trisomies
Trisomy 8 is the most common numerical abnormality in MDS, but overall, trisomies are less common than deletions 1.
Translocations
While translocations can occur in MDS, they are significantly less common than deletions. The IPSS-R prognostic system includes inv(3)/t(3;3), but these are relatively rare compared to deletions 1.
Inversions
Inversions are among the least common chromosomal abnormalities in MDS. The inv(3)(q21q26.2) is mentioned in guidelines but is relatively rare, occurring in approximately 1% of MDS cases 1.
Clinical Implications
The identification of specific deletions has important implications for:
- Diagnosis: Certain deletions like del(5q) can define specific MDS subtypes
- Prognosis: Chromosomal abnormalities are key components of the IPSS-R scoring system
- Treatment selection: For example, del(5q) MDS responds particularly well to lenalidomide
Diagnostic Approach
For suspected MDS, cytogenetic analysis should include:
- G-banded chromosome analysis as first-line testing (examining at least 20 metaphases)
- FISH analysis when conventional cytogenetics is unsuccessful or to clarify complex aberrations
- CMA (chromosomal microarray) analysis when appropriate to detect submicroscopic deletions
Summary
Based on the most current and authoritative guidelines, deletions represent the most common structural chromosomal abnormalities in MDS patients, with del(5q), del(7q), and del(20q) being particularly frequent. These deletions play crucial roles in MDS pathogenesis, classification, risk stratification, and treatment selection.