Portal de investigación
The relationship of TP53 R72P polymorphism to disease outcome and TP53 mutation in myelodysplastic syndromes
Fecha de publicación:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- McGraw KL
- Zhang LM
- Rollison DE
- Basiorka AA
- Fulp W
- Rawal B
- Jerez A
- Billingsley DL
- Lin HY
- Kurtin SE
- Yoder S
- Zhang Y
- Guinta K
- Mallo M
- Solé F
- Calasanz MJ
- González T
- Nevill TJ
- Haferlach T
- Smith AE
- Kulasekararaj A
- Mufti G
- Karsan A
- Maciejewski JP
- Sokol L
- Epling-Burnette PK
- Wei S
- List AF
Grupos
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 prolonged overall and progression-free 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.
Datos de la publicación
- ISSN/ISSNe:
- 2044-5385, 2044-5385
- Tipo:
- Article
- Páginas:
- -
- DOI:
- 10.1038/bcj.2015.11
- PubMed:
- 25768405
- Factor de Impacto:
- 1,926 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
Blood Cancer Journal SPRINGERNATURE
Citas Recibidas en Web of Science: 11
Documentos
- No hay documentos
Filiaciones
Campos de Estudio
Cita
McGraw KL,Zhang LM,Rollison DE,Basiorka AA,Fulp W,Rawal B,Jerez A,Billingsley DL,Lin HY,Kurtin SE,Yoder S,Zhang Y,Guinta K,Mallo M,Solé F,Calasanz MJ,CERVERA J,SUCH E,González T,Nevill TJ,Haferlach T,Smith AE,Kulasekararaj A,Mufti G,Karsan A,Maciejewski JP,Sokol L,Epling PK,Wei S,List AF. The relationship of TP53 R72P polymorphism to disease outcome and TP53 mutation in myelodysplastic syndromes. Blood Cancer J. 2015. 5. e291. IF:4,411. (1).