Chromosomal, Epigenetic, and Mutational Abnormalities

Myelodysplastic syndromes (MDS) are influenced by a number of chromosomal, epigenetic, or mutational abnormalities.1-3 Understanding these alterations can help healthcare professionals diagnose MDS and determine prognosis and treatment options.1


Adapted from: Bejar R et al. J Clin Oncol. 2011;29(5):504-515, and Issa JP. Blood. 2013;121(19):3811‑3817.

Chromosomal abnormalities

The anatomy of a chromosome is important in our understanding of MDS and the types of abnormalities that occur.


  • Each chromosome is made up of DNA. DNA winds around histones, which are proteins involved in holding the DNA in a compact shape4
  • The centromere helps keep the chromosomes properly aligned by serving as an attachment site for the halves of each chromosome. This gives the chromosome its characteristic shape4
  • The arms of the chromosome are on either side of the centromere. The short arm, or upper portion, is called the p arm. The long arm, or lower portion, is called the q arm. These are important when denoting the location of specific genes and abnormalities4

Different types of chromosomal abnormalities can occur. These may be changes to the chromosome structure or number, such as deletions, duplications, inversions, and translocations.5,6

Deletions, del or -( )7-10

A portion of, or the entire chromosome, is missing5

Inversions, inv( )

A portion of a chromosome breaks off, flips around, and reattaches in the wrong direction5

Duplications

A portion of a chromosome is duplicated, resulting in extra genetic material5

Translocations, t( )

Part of the chromosomal material transfers from one chromosome to another5

  • del(5q)
  • Monosomy 7 (-7)
  • del(7q)
  • del(20q)
  • Loss of Y (-Y)
  • del(11q)
  • del(12p)
  • del(3q)
  • i(17q)
  • inv(3)
  • Certain inversions are considered AML

  • inv(16)
  • Trisomy 8 (+8)
  • Trisomy 19 (+19)
  • t(3q)
  • Certain translocations are considered AML

  • t(8;21)
  • t(15;17)
Deletions, del or -( )7-10

A portion of, or the entire chromosome, is missing5

  • del(5q)
  • Monosomy 7 (-7)
  • del(7q)
  • del(20q)
  • Loss of Y (-Y)
  • del(11q)
  • del(12p)
  • del(3q)
Inversions, inv( )

A portion of a chromosome breaks off, flips around, and reattaches in the wrong direction5

  • i(17q)
  • inv(3)
  • Certain inversions are considered AML

  • inv(16)
Duplications

A portion of a chromosome is duplicated, resulting in extra genetic material5

  • Trisomy 8 (+8)
  • Trisomy 19 (+19)
Translocations, t( )

Part of the chromosomal material transfers from one chromosome to another5

  • t(3q)
  • Certain translocations are considered AML

  • t(8;21)
  • t(15;17)

AML, acute myeloid leukemia.

Chromosomal abnormalities are proven to be useful both diagnostically and prognostically.1

  • del(5q) has a favorable prognosis1
    • This is the most common chromosomal abnormality in MDS (incidence ≈15%)
  • del(7q) has a poor prognosis1
  • Trisomy 8 confers an intermediate risk, but patients may respond well to immunosuppressive therapy1
  • Loss of Y (-Y) and del(20q) have a favorable risk1

Epigenetic abnormalities

Epigenetic abnormalities are changes that alter gene expression but do not change the DNA sequence. Some examples that are often abnormal in MDS are2:

  • DNA methylation
  • Histone modification
  • Micro-RNA expression

These types of changes may co-exist with other cytogenetic changes and gene mutations.

Mutational abnormalities

Genetic abnormalities, or mutations, alter the sequence or expression of individual genes.1,3,11 One or more gene mutations are found in almost all MDS patients.1 Mutations in genes SF3B1, TET2, and ASXL1 are the most common, and dozens more have been found in recent years.1,3

Genetic mutations that alter the sequence or expression
of the individual genes1,3,11
  • TET2
  • ASXL1
  • RUNX1
  • TP53
  • DNMT3a
  • EZH2
  • RAS

Mutations within components of the spliceosome are found in up to 60% of MDS cases.11

Spliceosome mutations that alter the abundance or function of target genes through aberrant mRNA splicing3,11
  • SF3B1
  • SRSF2
  • U2AF1

See Molecular Analysis.

References: 1. Bejar R, Levine R, Ebert BL. Unraveling the molecular pathophysiology of myelodysplastic syndromes. J Clin Oncol. 2011;29(5):504-515. 2. Issa JP. The myelodysplastic syndrome as a prototypical epigenetic disease. Blood. 2013;121(19):3811-3817. 3. Montalban-Bravo G, Garcia-Manero G. Myelodysplastic syndromes: 2018 update on diagnosis, risk-stratification and management. Am J Hematol. 2018;93(1):129-147. 4. US National Library of Medicine. Genetics Home Reference. What is a chromosome? https://ghr.nlm.nih.gov/primer/basics/chromosome. Accessed October 18, 2018. 5. National Human Genome Research Institute. Chromosome abnormalities fact sheet. www.genome.gov/11508982. Accessed July 8, 2019. 6. Greenberg PL, Tuechler H, Schanz J, et al. Revised International Prognostic Scoring System for myelodysplastic syndromes. Blood. 2012;120(12):2454-2465. 7. Song Q, Peng M, Chu Y, Huang S. Techniques for detecting chromosomal aberrations in myelodysplastic syndromes. Oncotarget. 2017;8(37):62716-62729. 8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myelodysplastic Syndromes V.1.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed August 28, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 9. Schanz J, Tüchler H, Solé F, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol. 2012;30(8):820-829. 10. Garcia-Manero G. Myelodysplastic syndromes: 2015 update on diagnosis, risk-stratification and management. Am J Hematol. 2015;90(9):831-841. 11. Sperling AS, Gibson CJ, Ebert BL. The genetics of myelodysplastic syndrome: from clonal hematopoiesis to secondary leukemia. Nat Rev Cancer. 2017;17(1):5-19.