Interphase molecular cytogenetic screening for chromosomal abnormalities of prognostic significance in childhood acute lymphoblastic leukaemia: a UK Cancer Cytogenetics Group Study

Autor: G. Reza Jalali, Christine J. Harrison, Jonathan C. Strefford, Sarah Wright, Rachel L. Harris, Kerry E. Barber, Anthony V. Moorman, Mike Griffiths, Hazel M. Robinson, Zoë J. Broadfield, Louise Harewood, Adam R. M. Stewart, Fiona M. Ross, M Martineau, Kan L. Cheung
Rok vydání: 2005
Předmět:
Oncology
medicine.medical_specialty
Pathology
Adolescent
Oncogene Proteins
Fusion
Fusion Proteins
bcr-abl
Genes
abl
hemic and lymphatic diseases
Internal medicine
Acute lymphocytic leukemia
Proto-Oncogenes
medicine
Humans
Child
Interphase
neoplasms
In Situ Hybridization
Fluorescence
Chromosome Aberrations
Gene Rearrangement
Hematology
medicine.diagnostic_test
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Gene Amplification
Cytogenetics
breakpoint cluster region
Infant
Cancer
Histone-Lysine N-Methyltransferase
Gene rearrangement
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
medicine.disease
DNA-Binding Proteins
Child
Preschool
Core Binding Factor Alpha 2 Subunit
Cytogenetic Analysis
Hyperdiploidy
business
Myeloid-Lymphoid Leukemia Protein
Transcription Factors
Fluorescence in situ hybridization
Zdroj: British Journal of Haematology. 129:520-530
ISSN: 1365-2141
0007-1048
Popis: Summary Interphase fluorescence in situ hybridization (iFISH) was used independently to reveal chromosomal abnormalities of prognostic importance in a large, consecutive series of children (n = 2367) with acute lymphoblastic leukaemia (ALL). The fusions, TEL/AML1 and BCR/ABL, and rearrangements of the MLL gene occurred at frequencies of 22% (n = 447/2027) (25% in B-lineage ALL), 2% (n = 43/2027) and 2% (n = 47/2016) respectively. There was considerable variation in iFISH signal patterns both between and within patient samples. The TEL/AML1 probe showed the highest incidence of variation (59%, n = 524/884), which included 38 (2%) patients with clustered, multiple copies of AML1. We were thus able to define amplification of AML1 as a new recurrent abnormality in ALL, associated with a poor prognosis. Amplification involving the ABL gene, a rare recurrent abnormality confined to T ALL patients, was identified for the first time. The use of centromeric probes revealed significant hidden high hyperdiploidy of 33% and 59%, respectively, in patients with normal (n = 21/64) or failed (n = 32/54) cytogenetic results. The iFISH contributed significantly to the high success rate of 91% (n = 2114/2323) and the remarkable abnormality detection rate of 89% (n = 1879/2114). This study highlights the importance of iFISH as a complementary tool to cytogenetics in routine screening for significant chromosomal abnormalities in ALL.
Databáze: OpenAIRE
Externí odkaz: