title: Short telomere length and its correlation with gene mutations in myelodysplastic syndrome.
abstract: Telomere erosion can lead to genomic instability and cancer progression. It has been suggested that the shortest telomere, not the average telomere length (TL), is critical for cell viability. Some studies have shown shorter TL in myelodysplastic syndrome (MDS) patients but the critically short telomeres, the variability of TL within individual patient has not been evaluated. Thus, we aimed to investigate the TL of MDS patients and assessed the association of TL with recurrent genetic mutations in MDS.
  
  
  
  We measured the TL of bone marrow nucleated cells for diagnostic samples at a single-cell level by quantitative fluorescence in situ hybridization (Q-FISH) for 58 MDS patients and analyzed the minimum, median, average, standard deviation, average of the 0th to 10th percentile TL within a patient, and the proportion of cells with TL that is shorter than the lowest 10th percentile of the normal control (NC). The correlations of TL to clinical parameters, cytogenetic results, and genetic mutations were assessed.
  
  
  
  MDS patients showed eroded telomeres and narrow distribution compared to the NC (P < 0.001, P = 0.018, respectively). Patients with mutation showed significantly lesser cells with short TL, below the lowest 10th percentile of the NC (P = 0.017), but no differences in TL were found according to mutations/cytogenetic abnormalities except for CSF3R mutation. However, those patients with a high percentage (≥80 %) of cells with short TL showed poorer overall survival (P = 0.021), and this was an independent prognostic factor, along with TP53, U2AF1 mutation, and high BM blast count (P = 0.044, 0.001, 0.004, 0.012, respectively).
  
  
  
  The shortest TL, which determines the fate of the cell, was significantly shorter, and higher burden of cells with short TL were found in MDS, which correlated with poor survival, suggesting the need to measure TL in single cells by Q-FISH.
authors.affiliation: Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.|Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang Mee
authors.initials: SM
authors.lastname: Hwang
authors.affiliation: Department of Laboratory Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung Ah
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hee-Sue
authors.initials: HS
authors.lastname: Park
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Si Nae
authors.initials: SN
authors.lastname: Park
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyongok
authors.initials: K
authors.lastname: Im
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kwantae
authors.initials: K
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. soonlee@snu.ac.kr.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. soonlee@snu.ac.kr.
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells; D002869:Chromosome Aberrations; D005260:Female; D042822:Genomic Instability; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology*; D015996:Survival Rate; D016615:Telomere / Q000473:pathology*; D059506:Telomere Shortening; D055815:Young Adult
keywords: Mutation; Quantitative fluorescence in situ hybridization; Single cell; Telomere length