Genetic Analysis of Myelodysplastic Syndromes and Chromosome 5q31.2
Author Information
Author(s): Timothy A. Graubert, Michelle A. Payton, Jin Shao, Richard A. Walgren, Ryan S. Monahan, John L. Frater, Mark A. Walshauser, Mike G. Martin, Yumi Kasai, Matthew J. Walter
Primary Institution: Washington University School of Medicine
Hypothesis
Does haploinsufficiency of multiple chromosome 5q31.2 genes contribute to the pathogenesis of de novo myelodysplastic syndromes?
Conclusion
The study shows that haploinsufficiency of multiple genes in the 5q31.2 region is likely the relevant genetic consequence of deletions associated with myelodysplastic syndromes.
Supporting Evidence
- Deletions on chromosome 5q31.2 are common in myelodysplastic syndromes.
- Prior studies suggested haploinsufficiency of multiple genes in this region contributes to disease.
- The study found no somatic nucleotide changes in the analyzed MDS samples.
- Twelve novel single nucleotide polymorphisms were discovered.
- Gene expression levels of several genes were significantly reduced in MDS samples with deletions.
Takeaway
Scientists looked at genes on a specific part of chromosome 5 to see if missing parts could cause a blood disease called myelodysplastic syndrome. They found that losing many genes at once is more common than losing just one.
Methodology
The study involved total exonic gene resequencing and array comparative genomic hybridization on paired tumor and germline DNA samples from 46 de novo MDS patients.
Limitations
The study may not have detected all possible mutations due to cellular heterogeneity in MDS samples.
Participant Demographics
The study included 46 adult patients with de novo MDS, with a median age of 63.5 years, including 30 males and 16 females.
Statistical Information
P-Value
p=0.048 for CDC25C R70C and p=2.187E-10 for KLHL3 A157A
Confidence Interval
95% confidence interval for CDC25C R70C is 1.030–3.272 and for KLHL3 A157A is 5.914–1673
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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