Leuk Lymphoma  2001 Jul;42(3):473-9 

Lack of association between N-ras gene mutations and clinical prognosis in
Brazilian children with acute lymphoblastic leukemia.

Clementino NC, Yamamoto M, Viana MB, Figueiredo MS, Kerbauy J, Saad ST, Costa
FF.

Federal University of Sao Paulo, UNIFESP-EPM, Federal University of Minas
Gerais, UFMG, S. Paulo, Brazil.

Point mutations in codons 12, 13 and 61 of the N-ras proto-oncogene have been
detected in several human malignancies. We studied 170 patients with acute
lymphoblastic leukemia (ALL), treated from 1988 to 1994 according to a protocol
derived from BFM-83 studies, in order to evaluate the incidence and prognostic
significance of mutations in this gene in childhood ALL. DNA was extracted from
bone marrow smears at diagnosis and amplified by polymerase chain reaction
(PCR). After screening with SSCP, PCR products were hybridized with allele
specific probes and, in some cases, cloned in a pMOS Blue T vector and
sequenced. Exon 2 was also studied in 101 children. Our results showed 4% of
mutations in codons 12 and 13 and 2% in exon 2. Similar to a previous report, we
identified 7% of mutations among children who were studied for both exons. A new
mutation in codon 64 of the N-ras gene was detected in one patient. No
significant clinical differences between patients with and without mutations
were detected (sex, age, leukocyte counts at diagnosis, nutritional status, and
risk factor according to the BFM protocol). Children with mutations in codons 12
and 13 showed significantly higher reactivity to PAS staining on blast cells
than children with a wild type N-ras gene configuration. Comparison of overall-
and recurrence-free survival did not show significant difference between groups
with and without mutations. Our results suggest that mutations in the ras gene
are infrequent in children with ALL at diagnosis and seem to be of low
prognostic value.

PMID: 11699412 [PubMed - indexed for MEDLINE]