The relationship of TP53 R72P polymorphism to disease outcome and TP53 mutation in myelodysplastic syndromes
Palabras clave : 
Myelodysplastic syndrome
Cancer
TP53 R72P polymorphism
Fecha de publicación: 
2015
ISSN: 
2044-5385
Nota: 
This is an open access article distributed under the Creative Commons: Atribution License (cc BY)
Cita: 
McGraw KL, Zhang LM, Rollison DE, Basiorka AA, Fulp W, Rawal B, et al. The relationship of TP53 R72P polymorphism to disease outcome and TP53 mutation in myelodysplastic syndromes. Blood Cancer Journal 2015;5(e291):1-7
Resumen
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 prolonged overall and progressionfree survival and non-terminal interstitial deletions that excluded 5q34, whereas G-allele homozygozity was associated with inferior outcome and terminal deletions involving 5q34 (P = 0.05). These findings comprise the largest MDS R72P SNP analysis.

Ficheros en este registro:
Fichero: 
pdf.pdf
Descripción: 
Tamaño: 
939,48 kB
Formato: 
Adobe PDF


Los ítems de Dadun están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.