Mutational analysis of therapy-related myelodysplastic syndromes and acute myelogenous leukemia.
Therapy-related myelodysplastic syndromes and acute myelogenous leukemia comprise a poor-risk subset of myelodysplastic syndromes and acute myelogenous leukemia. Large-scale mutation profiling efforts in de novo myelodysplastic syndromes have identified mutations that correlate with clinical features, but such mutations have not been investigated in therapy-related myelodysplastic syndromes and acute myelogenous leukemia. Genomic DNA from 38 patient samples were subjected to high throughput polymerase chain reaction and sequenced for TP53, TET2, DNMT3A, ASXL1, IDH1, IDH2, EZH2, EED, SUZ12, RBBP4, SRSF2, U2AF35, and SF3B1. We identified somatic mutations in 16 of 38 (42%) patients. TP53 mutations were the most common lesion, detected in 8 of 38 (21%) patients, followed by TET2 in 4 of 38 (10.5%). Cases with a TP53 mutation or loss of the TP53 locus had a worse overall survival compared to those with wild-type TP53 (8.8 vs. 37.4 months; P=0.0035).
Department of Medicine, Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Alan H
AH
Shih
Stephen S
SS
Chung
Emily K
EK
Dolezal
Su-Jiang
SJ
Zhang
Omar I
OI
Abdel-Wahab
Christopher Y
CY
Park
Stephen D
SD
Nimer
Ross L
RL
Levine
Virginia M
VM
Klimek
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D009190:Myelodysplastic Syndromes / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D011878:Radiotherapy / Q000009:adverse effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016159:Tumor Suppressor Protein p53