While cancers with one of these aberrations behaved only marginally different from cancers with none, disease outcome was markedly worse in cancers with two or more aberrations as compared to those with only one aberration (p = 0.0002).
With two exceptions, these aberrations were mutually exclusive.
With some of these aberrations the expression of tumour relevant genes may be correlated, such as RB1 (13q), CDH1 (16q), SIAH1 (16q), and TP53 (17p).
The Kaplan-Meier analysis further showed significantly shorter survival for patients with tumors containing gain of the 7q region, or loss of the 9p, 9q, or 14q regions (log-rank P=0.008, 0.0004, 0.0003, and 0.001, respectively) compared with cases without these aberrations (Figs. 2A D).
The frequency of cytogenetic chromosomal aberrations, such as translocations and hyperdiploidy in this group of leukemia cases, could not be compared with the frequency of these aberrations found in the general population of children with ALL because, in most cases, bone marrow was not stored, testing was not done, or cells did not divide for metaphase analysis.
Correcting these aberrations with nanometre precision requires a dedicated design of a deformable mirror and a measurement set-up that can validate the design.
Loss of 9p21.3p24.1 was the most prominent of these aberrations with the highest odds ratio for metastatic risk and was linked to shorter CSS only on univariate analysis.
It has been suggested that especially at high acute doses, a fraction of the initial symmetrical translocations is lost due to coincident occurrence of these aberrations with unstable aberrations and/or due to the loss of genetic material in fragments too small to be detected by FISH.
"He asked, 'Could viruses have something to do with these chromosomal aberrations?' " said Dr. Eugene O. Major of the National Institute of Neurological Disorders and Stroke, who collaborated with Dr. Neel on the work.
The manner in which the ASXL1 mutation was associated with these genetic aberrations in the MDS pathogenesis needs further investigation.
