Correlation of N-ras point mutations with specific chromosomal abnormalities in primary myelodysplastic syndrome
Autor: | Eliana Abdelhay, Teresa de Souza Fernandez, Daniel Tabak, Jamison M. de Souza, Maria Luiza Macedo Silva |
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Rok vydání: | 1998 |
Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Pathology Adolescent Chronic myelomonocytic leukemia Aneuploidy Chromosome Disorders Biology Proto-Oncogene Mas hemic and lymphatic diseases medicine Humans Point Mutation Child Aged Aged 80 and over Chromosome Aberrations Chromosome 7 (human) Point mutation Cytogenetics Infant Myeloid leukemia Hematology Middle Aged medicine.disease Leukemia Cell Transformation Neoplastic Genes ras Oncology Child Preschool Myelodysplastic Syndromes Cancer research Female Trisomy |
Zdroj: | Leukemia Research. 22:125-134 |
ISSN: | 0145-2126 |
Popis: | A cytogenetic and N-ras point mutation study was done in patients with primary myelodysplastic syndrome (MDS) from Rio de Janeiro, Brazil, in order to evaluate the progression of preleukemic states to overt leukemia. Cytogenetic analysis was performed in 50 patients with MDS and clonal chromosomal abnormalities were detected in 19 (38%) of them. Patients with refractory anemia (RA) or with ringed sideroblasts (RARS) presented normal karyotypes or single abnormalities as del(5q) or − Y, while patients in more advanced states as RA with excess of blasts (RAEB), RAEB in transformation (RAEB-t) and chronic myelomonocytic leukemia (CMML) showed complex karyotypes and single abnormalities involving chromosomes 7 or 8, which were related to poor prognosis and elevated risk of transformation to acute myeloid leukemia (AML). The frequency of ras activation was studied in these 50 patients with MDS. Samples of bone marrow were screened for oncogenic point mutations by DNA amplification followed by oligonucleotide hybridization analysis (PCR-ASO) at codon 12 of N-ras proto-oncogene. We detected N-ras point mutations in 21 patients (42%). Progression from MDS to AML was observed in 9 patients (18%). The correlation analysis between N-ras point mutations and specific chromosomal abnormalities indicated that although mutated N-ras was found in cells with del(5q) and monosomy 7, cells with those abnormalities and normal N-ras were also identified. Otherwise trisomy of chromosome 8 showed a correlation with N-ras point mutations and in all cases, patients showed progression of MDS to AML during the follow-up study. MDS comprises a heterogeneous group of hematopoietic disorders and probably several steps are implicated in the evolution to AML. In this work we suggest that one possible pathway of leukemogenesis in MDS includes N-ras point mutations in association with trisomy of chromosome 8. |
Databáze: | OpenAIRE |
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