The relationship of TP53 R72P polymorphism to disease outcome and TP53 mutation in myelodysplastic syndromes

Blood Cancer Journal
K McGrawA List

Abstract

Nonsynonymous TP53 exon 4 single-nucleotide polymorphism (SNP), R72P, is linked to cancer and mutagen susceptibility. R72P associations with specific cancer risk, particularly hematological malignancies, have been conflicting. Myelodysplastic syndrome (MDS) with chromosome 5q deletion is characterized by erythroid hypoplasia arising from lineage-specific p53 accumulation resulting from ribosomal insufficiency. We hypothesized that apoptotically diminished R72P C-allele may influence predisposition to del(5q) MDS. Bone marrow and blood DNA was sequenced from 705 MDS cases (333 del(5q), 372 non-del(5q)) and 157 controls. Genotype distribution did not significantly differ between del(5q) cases (12.6% CC, 38.1% CG, 49.2% GG), non-del(5q) cases (9.7% CC, 44.6% CG, 45.7% GG) and controls (7.6% CC, 37.6% CG, 54.8% GG) (P=0.13). Allele frequency did not differ between non-del(5q) and del(5q) cases (P=0.91) but trended towards increased C-allele frequency comparing non-del(5q) (P=0.08) and del(5q) (P=0.10) cases with controls. Median lenalidomide response duration increased proportionate to C-allele dosage in del(5q) patients (2.2 (CC), 1.3 (CG) and 0.89 years (GG)). Furthermore, C-allele homozygosity in del(5q) was associated with prol...Continue Reading

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Citations

Oct 27, 2016·Experimental Hematology·Fabrice DanjouMaurizio Longinotti
Dec 24, 2018·European Journal of Haematology·Jung-Hoon LeeDavid A Sallman
May 24, 2018·Cardiovascular & Hematological Disorders Drug Targets·Ota Fuchs
May 18, 2020·International Journal of Molecular Sciences·Cosimo CumboFrancesco Albano
May 22, 2017·Journal of Medical Case Reports·Fernando Barroso DuartePaulo Roberto Leitão de Vasconcelos

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Methods Mentioned

BETA
MDS
genotyping

Software Mentioned

SAS

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