PMID- 7707106
OWN - NLM
STAT- MEDLINE
DCOM- 19950510
LR  - 20170210
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 13
IP  - 4
DP  - 1995 Apr
TI  - Clinical significance of p53 mutations in newly diagnosed Burkitt's lymphoma and 
      acute lymphoblastic leukemia: a report of 48 cases.
PG  - 812-20
AB  - PURPOSE: To correlate the presence of p53 mutations and initial characteristics, 
      response to chemotherapy, and survival in newly diagnosed Burkitt's lymphoma (BL) 
      and Burkitt's acute lymphoblastic leukemia (L3 ALL). PATIENTS AND METHODS: 
      Forty-eight patients with newly diagnosed BL or L3 ALL, most of whom were treated 
      with very intensive regimens, including early CNS disease treatment, were 
      studied. Detection of p53 mutations was made by single-strand conformation 
      polymorphism (SSCP) analysis of exons 5 to 8 of the gene, and mutations were 
      determined by direct sequencing of exons with abnormal SSCP findings. Comparison 
      of outcome between mutated and nonmutated cases was made in all patients and also 
      after excluding five patients who received therapeutic regimens considered as 
      suboptimal and one patient who died of AIDS while in complete remission (CR), as 
      those six patients had no p53 mutations. RESULTS: A point mutation was found in 
      nine patients (19%), and consisted of a missense mutation in seven and a 
      chain-terminating mutation in two. SSCP, sequence, and cytogenetic analysis 
      strongly suggested that eight of nine patients with mutations had retained the 
      normal p53 allele, which had been lost in the remaining patient. These findings 
      were confirmed by fluorescence-in-situ hybridization (FISH) with a p53-specific 
      probe in two patients, including the one who had lost the normal p53 allele. 
      Unexpectedly, mutations were significantly less frequent in patients with 
      disseminated disease, ie, L3 ALL or stage IV BL (four of 35, 11%), than in more 
      localized forms, ie, BL stage I, II, or III (five of 13, 38%) (P = .03). CR rates 
      were similar in mutated (78%) and nonmutated cases (78%). The actuarial 
      disease-free interval (DFI) after 12 months and actuarial survival rates after 24 
      months were 49% and 66%, respectively, in patients with mutations, and 73% and 
      48%, respectively, those without mutations. The differences were not significant. 
      CONCLUSION: Our findings suggest that, contrary to what is seen in most other 
      neoplasias, p53 mutations in newly diagnosed BL and L3 ALL are not associated 
      with extensive tumor mass or poor response to intensive therapeutic regimens. It 
      is hypothesized that this difference with most tumors could be due to the fact 
      that p53 mutations in BL and L3 ALL are generally associated with persistence of 
      a normal residual p53 allele, contrary to what is observed in the majority of 
      tumors.
FAU - Preudhomme, C
AU  - Preudhomme C
AD  - Inserm U124, Laboratoire d'Hematologie A, Centre Oscar Lambret, Lille, France.
FAU - Dervite, I
AU  - Dervite I
FAU - Wattel, E
AU  - Wattel E
FAU - Vanrumbeke, M
AU  - Vanrumbeke M
FAU - Flactif, M
AU  - Flactif M
FAU - Lai, J L
AU  - Lai JL
FAU - Hecquet, B
AU  - Hecquet B
FAU - Coppin, M C
AU  - Coppin MC
FAU - Nelken, B
AU  - Nelken B
FAU - Gosselin, B
AU  - Gosselin B
AU  - et al.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
SB  - IM
MH  - Actuarial Analysis
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Base Sequence
MH  - Burkitt Lymphoma/drug therapy/*genetics/mortality
MH  - Child
MH  - Child, Preschool
MH  - Disease-Free Survival
MH  - Female
MH  - Genes, p53/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - *Point Mutation
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/*genetics/mortality
MH  - Survival Rate
EDAT- 1995/04/01 00:00
MHDA- 1995/04/01 00:01
CRDT- 1995/04/01 00:00
PHST- 1995/04/01 00:00 [pubmed]
PHST- 1995/04/01 00:01 [medline]
PHST- 1995/04/01 00:00 [entrez]
AID - 10.1200/JCO.1995.13.4.812 [doi]
PST - ppublish
SO  - J Clin Oncol. 1995 Apr;13(4):812-20. doi: 10.1200/JCO.1995.13.4.812.