Chromosomal alterations of pediatric malignancy in a West Texas population

Aditya Rajan BS, Sahil Tonk, Chhanda Bose PhD, Sharda P. Singh PhD, Sriman Swarup MD, Tejaswini P Reddy BS, Santosh Chavali BS, Kishore Bhende MD, Philip T. Palade PhD, Ashly Hindle PhD, Meenakshi Darden MD, Vijay Tonk PhD, Sanjay Awasthi MD


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.

Keywords: ADAM32, TACC1, KAT6A, TM2D2, 8p11.21

Article citation: Rajan A, Tonk S, Bose C, Singh SP, Swarup S, Reddy TP, Chavali S, Bhende K, Palade PT, Hindle A, Darden M, Tonk V, Awasthi S. Chromosomal alterations of pediatric malignancy in a West Texas population. The Southwest Respiratory and Critical Care Chronicles 2020;8(33):7–20
From: Departments of Internal Medicine (AR, ST, CB, SPS, SS, AH, SA) and Pediatrics (TPR, SC, KB, VT), Texas Tech University Health Sciences Center, Lubbock, Texas; Department of Pharmacology and Toxicology (PTP), University of Arkansas for Medical Sciences, Little Rock, AR; McGovern Medical School of the University of Texas Health Sciences Center (MD), Houston TX.
Submitted: 1/7/2020
Accepted: 1/21/2020
Reviewer: Kenneth Nugent MD
Conflicts of interest: none
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