Retrospective analysis of FFPE based Wilms' Tumor samples through copy number and somatic mutation related Molecular Inversion Probe Based Array.
In this report, retrospectively, we analyzed fifteen histo-pathologically characterized FFPE based Wilms' Tumor (WT) samples following an integrative approach of copy number (CN) and loss of heterozygosity (LOH) imbalances. The isolated-DNA was tested on CN and somatic-mutation related Molecular-Inversion-Probe based-Oncoscan Array™ and was analyzed through Nexus-Express OncoScan-3.0 and 7.0 software. We identified gain of 3p13.0-q29, 4p16.3-14.0, 7, 12p13.33-q24.33, and losses of 1p36.11-q44, 11p15.5-q25, 21q 22.2-22.3 and 22q11.21-13.2 in six samples (W1-6) and validated them in nine more samples (W7-9, W12-15, W17-18). Some observed that discrete deletions (1p, 1q, 10p, 10q, 13q, 20p) were specific to our samples. Maximum-LOH was observed in Ch11 as reported in previous studies. However, LOH was also observed in different regions of Ch7 including some cancer genes. The identified LOH-regions (1q21.2-q21.3, 2p24.1-23.3, 2p24.3-24.3, 3p21.3-21.1, 4p16.3, 7p11.2-p11.1, 7q31.2-31.32, 7q34-q35 and Ch 8) in W1-W6 were also validated in W7-9, W12-15 and W18. In addition, previously reported LOH of 1p and 16q region was also observed in our cases. The proven and novel onco (OG)- and tumor-suppressor genes (TSGs) involved in the CNV regions affected the major pathways like Chromatin Modification, RAS, PI3K; RAS in 14/15 cases, NOTCH/TGF-β and Cell Cycle Apoptosis in 10/15 cases, APC in 9/15 cases and Transcriptional Regulation in 7/15 cases, PI3K and genome maintenance in 6/15 cases. This exhaustive profiling of OG and TG may help in prognosis and diagnosis of the disease after validation of all the relevant results, especially the novel ones, obtained in this research in a larger number of samples.
Advanced Molecular Science Research Center (Center for Advanced Research), King George's Medical University, Lucknow 226 003, India. Electronic address: neetuaashi@yahoo.com.
Neetu
N
Singh
Imperial Life Sciences, 463 Phase City 2nd, Sector 37, Gurgaon, Haryana 122001, India.
Dinesh K
DK
Sahu
Department of Pathology, King George's Medical University, Lucknow 226 003, India.
Madhumati
M
Goel
Department of Surgical Oncology, King George's Medical University, Lucknow, Uttar Pradesh, India226 003.
Ravi
R
Kant
Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India.
Devendra K
DK
Gupta
D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002843:Chromatin / Q000235:genetics; D007446:Chromosome Inversion / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D016678:Genome / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity / Q000235:genetics; D046228:Microarray Analysis / Q000379:methods; D015335:Molecular Probes / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D012189:Retrospective Studies; D012984:Software; D016212:Transforming Growth Factor beta / Q000235:genetics; D009396:Wilms Tumor / Q000235:genetics*
D002843:Chromatin; D015335:Molecular Probes; D016212:Transforming Growth Factor beta; D019869:Phosphatidylinositol 3-Kinases
Copy number variation; LOH; Oncogene; Oncoscan array; Tumor-suppressor genes; Wilms' Tumor