PMID- 33486841
OWN - NLM
STAT- MEDLINE
DCOM- 20220310
LR  - 20220310
IS  - 1098-2264 (Electronic)
IS  - 1045-2257 (Linking)
VI  - 60
IP  - 6
DP  - 2021 Jun
TI  - Unbalanced translocation der(5;17) resulting in a TP53 loss as recurrent 
      aberration in myelodysplastic syndrome and acute myeloid leukemia with complex 
      karyotype.
PG  - 452-457
LID - 10.1002/gcc.22938 [doi]
AB  - A complex karyotype, detected in myelodysplastic syndrome (MDS) and acute myeloid 
      leukaemia (AML), is associated with a reduced median survival. The most frequent 
      chromosomal aberrations in complex karyotypes are deletions of 5q and 17p 
      harboring the tumor suppressor gene TP53. The unbalanced translocation der(5;17) 
      involving chromosome 5q and 17p is a recurrent aberration in MDS/AML, resulting 
      in TP53 loss. We analyzed the karyotypes of 178 patients with an unbalanced 
      translocation der(5;17) using fluorescence R-/G-banding analysis. Whenever 
      possible, fluorescence in situ hybridization (FISH) (n = 138/141), multicolor 
      FISH (n = 8), telomere length measurement (n = 9), targeted DNA sequencing (n = 
      13), array-CGH (n = 7) and targeted RNA sequencing (n = 2) were conducted. The 
      der(5;17) aberration was accompanied with loss of genetic material in 7q (53%), 
      -7 (27%), gain of 21q (29%), +8 (17%) and - 18 (16%) and all analyzed patients (n 
      = 13) showed a (likely) pathogenic variant inTP53. The der(5;17) cohort showed 
      significantly shortened telomeres in comparison to the healthy age-matched 
      controls (P < .05), but there was no significant telomere shortening in 
      comparison to MDS/AML patients with a complex karyotype without der(5;17). No 
      fusion genes resulted from the unbalanced translocation. This study demonstrates 
      that the unbalanced translocation der(5;17) is associated with a biallelic 
      inactivation of TP53 due to a deletion of TP53 in one allele and a pathogenic 
      variant of the second TP53 allele. Since the breakpoints are located within 
      (near-) heterochromatic regions, alterations of DNA methylation or histone 
      modifications may be involved in the generation of der(5;17).
CI  - (c) 2021 The Authors. Genes, Chromosomes & Cancer published by Wiley Periodicals 
      LLC.
FAU - Warnstorf, Daria
AU  - Warnstorf D
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
FAU - Bawadi, Randa
AU  - Bawadi R
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
FAU - Schienke, Andrea
AU  - Schienke A
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
FAU - Strasser, Renate
AU  - Strasser R
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
FAU - Schmidt, Gunnar
AU  - Schmidt G
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
FAU - Illig, Thomas
AU  - Illig T
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
FAU - Tauscher, Marcel
AU  - Tauscher M
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
FAU - Thol, Felicitas
AU  - Thol F
AD  - Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, Hannover, Germany.
FAU - Heuser, Michael
AU  - Heuser M
AD  - Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, Hannover, Germany.
FAU - Steinemann, Doris
AU  - Steinemann D
AUID- ORCID: 0000-0001-8797-0816
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
FAU - Davenport, Claudia
AU  - Davenport C
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
FAU - Schlegelberger, Brigitte
AU  - Schlegelberger B
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
FAU - Behrens, Yvonne Lisa
AU  - Behrens YL
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
FAU - Gohring, Gudrun
AU  - Gohring G
AUID- ORCID: 0000-0002-0863-8645
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210219
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Abnormal Karyotype
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Child
MH  - Chromosomes, Human, Pair 17/*genetics
MH  - Chromosomes, Human, Pair 5/*genetics
MH  - Female
MH  - Humans
MH  - Leukemia, Myeloid, Acute/*genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Myelodysplastic Syndromes/*genetics/pathology
MH  - *Translocation, Genetic
MH  - Tumor Suppressor Protein p53/*genetics
OTO - NOTNLM
OT  - AML
OT  - MDS
OT  - TP53
OT  - complex karyotype
OT  - unbalanced translocation
EDAT- 2021/01/25 06:00
MHDA- 2022/03/11 06:00
CRDT- 2021/01/24 20:54
PHST- 2021/01/08 00:00 [revised]
PHST- 2020/08/14 00:00 [received]
PHST- 2021/01/11 00:00 [accepted]
PHST- 2021/01/25 06:00 [pubmed]
PHST- 2022/03/11 06:00 [medline]
PHST- 2021/01/24 20:54 [entrez]
AID - 10.1002/gcc.22938 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2021 Jun;60(6):452-457. doi: 10.1002/gcc.22938. Epub 
      2021 Feb 19.