Molecular karyotyping and gene expression analysis in childhood cancer patients

Abstract

The genetic etiology of sporadic childhood cancer cases remains unclear. We recruited a cohort of 20 patients who survived a childhood malignancy and then developed a second primary cancer (2N), and 20 carefully matched patients who survived a childhood cancer without developing a second malignancy (1N). Twenty matched cancer-free (0N) and additional 1000 (0N) GHS participants served as controls. Aiming to identify new candidate loci for cancer predisposition, we compared the genome-wide DNA copy number variations (CNV) with the RNA-expression data obtained after in vitro irradiation of primary fibroblasts. In 2N patients, we detected a total of 142 genes affected by CNV. A total of 53 genes of these were not altered in controls. Six genes (POLR3F, SEC23B, ZNF133, C16orf45, RRN3, and NTAN1) that we found to be overexpressed after irradiation were also duplicated in the genome of the 2N patients. For the 1N collective, 185 genes were affected by CNV and 38 of these genes were not altered in controls. Five genes (ZCWPW2, SYNCRIP, DHX30, DHRS4L2, and THSD1) were located in duplicated genomic regions and exhibited altered RNA expression after irradiation. One gene (ABCC6) was partially duplicated in one 1N and one 2N patient. Analysis of methylation levels of THSD1 and GSTT2 genes which were detected in duplicated regions and are frequently aberrantly methylated in cancer showed no changes in patient’s fibroblasts. In summary, we describe rare and radiation-sensitive genes affected by CNV in childhood sporadic cancer cases, which may have an impact on cancer development. Key messages • Rare CNV’s may have an impact on cancer development in sporadic, non-familial, non-syndromic childhood cancer cases. • In our cohort, each patient displayed a unique pattern of cancer-related gene CNVs, and only few cases shared similar CNV. • Genes that are transcriptionally regulated after radiation can be located in CNVs in cancer patients and controls. • THSD1 and GSTT2 methylation is not altered by CNV.

Comprehensive analysis of histone methylation modification regulators for predicting prognosis and drug sensitivity in lung adenocarcinoma

“…Given the contradictory roles of SGF29 in cancers, it is worth initiating further studies. ZCWPW2 (zinc finger CW-type PWWP domain protein 2), which is the reader of H3K4me3 ( Danuta et al, 2020 ), was identified as an antioncogene in our study. Until now, the functions of ZCWPW2 in tumors have not been fully studied.…”

The Ntan1 gene is expressed in perineural glia and neurons of adult Drosophila

“…Finally, it has been shown that the Ntan1 gene performs numerous functions in vertebrates and defects in the gene can have serious effects at the level of the organism. Thus, alterations in the Ntan1 gene expression have been associated with different types of memory and social behavior 32 , 33 , sporadic childhood cancer 34 and risk of schizophrenia 35 . Therefore, studies in Drosophila using all the new tools available achieve a greater projection in determining the cellular basis of these phenotypes, which is necessary for their possible reversion.…”

KRAB-ZFP Transcriptional Regulators Acting as Oncogenes and Tumor Suppressors: An Overview

“…High levels of ZNF133 have also been detected in irradiated fibroblasts and in childhood cancer survivors that developed second primary cancer. This overexpression was linked to copy number variation events [ 132 ]. ZNF133 was also recognized as a factor associated with Alagille syndrome—a genetic disease related to the disruptions in the Notch signaling pathway that predisposes to pediatric HCC [ 133 ].…”