Array comparative genome hybridization analysis of acute lymphoblastic leukaemia and acute megakaryoblastic leukaemia in patients with Down syndrome.
Twenty-five cases of B-cell precursor acute lymphoblastic leukaemia (ALL) from Down syndrome (DS) patients were analyzed using array comparative genomic hybridization (aCGH) and compared with two other subgroups of non-DS patients with ALL; five cases with high-hyperdiploidy (HH) and nine cases with ETV6-RUNX1 positive clones. Seven cases of DS-acute megakaryoblastic leukaemia (AMKL) were also included, DS-ALL cases showed relatively stable karyotypes with cryptic losses and gains that most frequently involved chromosomes X, 1, 2, 9, 11, 16, and 17. The most consistent change involved a deletion in 2p, spanning region Chr2:88273220-91084234, which in some cases appeared to be homozygous. ALL from non-DS patients showed a similar overall karyotypic stability, although gains of chromosome 21 were infrequent in the ETV6-RUNX1 positive cases. The most consistent change in this group involved a 12p deletion, where Chr12:10383878-16017619 defined the common region of overlap. All HH-ALL karyotypes showed variable gains of chromosome 21. This overall analysis supports the suggestion that, although constitutional trisomy 21 predisposes to ALL/AMKL, the cytogenetic changes associated with DS-ALL in particular, are most similar to those found in non-DS ETV6-RUNX1 positive ALL. The HH-ALL group, however, undergoes distinct karyotypic evolution not dependent on chromosome translocation/deletion events.
Lo
Ken C
KC
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Chalker
Jane
J
Strehl
Sabine
S
Neat
Michael
M
Smith
Owen
O
Dastugue
Nicole
N
Kearney
Lyndal
L
Izraeli
Shai
S
Kempski
Helena
H
Cowell
John K
JK
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D004314:Down Syndrome / Q000235:genetics*; D005260:Female; D006801:Humans; D007621:Karyotyping; D007947:Leukemia, Megakaryoblastic, Acute / Q000235:genetics*; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011003:Ploidies; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D055815:Young Adult; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein