Chromosomal alterations of pediatric malignancy in a West Texas population

Abstract

Background: Comparative genomic hybridization (CGH) microarrays are used for
genome-wide evaluation of copy number variations (CNV) of known prognostic significance;
however, unannotated variants of uncertain significance (VUS) are frequently present. To
identify potentially actionable targets, we retrospectively analyzed VUS loci using CGH data
from 192 cases of cancer or genetic disorders treated at TTUHSC.
Methods: DNA was hybridized onto CytoSure Constitution V3 arrays, scanned with the
Agilent microarray D scanner, and analyzed by CytoSure Interpret Software.
Results: We found 794 distinct CNVs, the most frequent being 14q32.22 (112
rearrangements), 14q11.2 (100), 8p11.2 (98), 15q11.1-q11.2 (83), and 8p23.1 (77). In particular,
8p11.22 alterations were found in many pediatric tumors, with gain/loss ratio of 4.7. Linkage of
TACC1, TM2D2, KAT6A and ADAM32 was indicated by a similar 5-year survival rate of 75.3%
(n = 253), which was greater than in unaltered cases (62.2%, n = 15,809 cases) in The Cancer
Genome Atlas database.
Conclusion: Knockdown of genes occurring at variants of uncertain significance (VUS)
loci may help identify new therapy targets.