A rare PALB2 germline variant causing G2/M cell cycle arrest is associated with isolated myelosarcoma in infancy.
PALB2
extramedullary myelogenous leukaemia
myeloid sarcoma
tumour suppressor
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
12
05
2021
received:
18
02
2021
accepted:
01
07
2021
pubmed:
13
8
2021
medline:
17
3
2022
entrez:
12
8
2021
Statut:
ppublish
Résumé
Isolated myelosarcoma of infancy is a rare presentation of acute myelogenous leukaemia (AML). Because of its rarity and early onset in infancy underlying genetic predisposition is potentially relevant in disease initiation. We report an oncologic emergency in an infant with thoracic and intraspinal aleukaemic myeloid sarcoma causing acute myelon compression and lower leg palsy. Whole-exome sequencing of the patient's germline DNA identified a rare PALB2 (OMIM 610355) variant (p.A1079S), which is located in a domain critical for the gene's proper function within the homology-directed repair pathway. In line with potential DNA damage repair defects mediated by the PALB2 deregulation, the patient's fibroblasts showed increased sensitivity towards radiation and DNA intercalating agents. Therefore, we suggest PALB2 p.A1079S as a pathogenic variant potentially contributing to the here observed patient phenotype.
Sections du résumé
BACKGROUND
Isolated myelosarcoma of infancy is a rare presentation of acute myelogenous leukaemia (AML). Because of its rarity and early onset in infancy underlying genetic predisposition is potentially relevant in disease initiation.
METHODS AND RESULTS
We report an oncologic emergency in an infant with thoracic and intraspinal aleukaemic myeloid sarcoma causing acute myelon compression and lower leg palsy. Whole-exome sequencing of the patient's germline DNA identified a rare PALB2 (OMIM 610355) variant (p.A1079S), which is located in a domain critical for the gene's proper function within the homology-directed repair pathway. In line with potential DNA damage repair defects mediated by the PALB2 deregulation, the patient's fibroblasts showed increased sensitivity towards radiation and DNA intercalating agents.
CONCLUSION
Therefore, we suggest PALB2 p.A1079S as a pathogenic variant potentially contributing to the here observed patient phenotype.
Identifiants
pubmed: 34382369
doi: 10.1002/mgg3.1746
pmc: PMC8457705
doi:
Substances chimiques
Fanconi Anemia Complementation Group N Protein
0
PALB2 protein, human
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1746Informations de copyright
© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
Références
Pediatr Blood Cancer. 2007 Apr;48(4):393-8
pubmed: 16550530
Mol Cell. 2006 Jun 23;22(6):719-729
pubmed: 16793542
Nat Genet. 2007 Feb;39(2):159-61
pubmed: 17200672
Leuk Lymphoma. 2002 Mar;43(3):565-74
pubmed: 12002760
Clin Lymphoma Myeloma Leuk. 2018 Jun;18(6):e249-e254
pubmed: 29680411
Trends Biochem Sci. 2015 Nov;40(11):701-714
pubmed: 26439531
Atlas Genet Cytogenet Oncol Haematol. 2018 Apr;22(12):484-490
pubmed: 31413733
N Engl J Med. 2014 Aug 7;371(6):497-506
pubmed: 25099575
Nat Genet. 2007 Feb;39(2):162-4
pubmed: 17200671
Nat Rev Cancer. 2011 Dec 23;12(1):68-78
pubmed: 22193408
Cell Rep. 2014 Feb 13;6(3):553-64
pubmed: 24485656
J Pediatr Hematol Oncol. 2003 Oct;25(10):760-8
pubmed: 14528097
Leukemia. 2001 Jan;15(1):46-9
pubmed: 11243398
EMBO Rep. 2011 Jul 01;12(7):705-12
pubmed: 21637299
Breast Cancer Res Treat. 2015 Dec;154(3):463-71
pubmed: 26564480
Pediatr Blood Cancer. 2017 Dec;64(12):
pubmed: 28333413
Int J Cancer. 2021 Jul 26;:
pubmed: 34310709
Oncogene. 2014 Oct 2;33(40):4803-12
pubmed: 24141787
Mol Genet Genomic Med. 2021 Sep;9(9):e1746
pubmed: 34382369