Methylation and expression analyses of Pallister-Killian syndrome reveal partial dosage compensation of tetrasomy 12p and hypomethylation of gene-poor regions on 12p

Abstract

To ascertain the epigenomic features, i.e., the methylation, non-coding RNA, and gene expression patterns, associated with gain of i(12p) in Pallister-Killian syndrome (PKS), we investigated single cell clones, harboring either disomy 12 or tetrasomy 12p, from a patient with PKS. The i(12p)-positive cells displayed a characteristic expression and methylation signature. Of all the genes on 12p, 13% were overexpressed, including the ATN1, COPS7A, and NECAP1 genes in 12p13.31, a region previously implicated in PKS. However, the median expression fold change (1.3) on 12p was lower than expected by tetrasomy 12p. Thus, partial dosage compensation occurs in cells with i(12p). The majority (89%) of the significantly deregulated genes were not situated on 12p, indicating that global perturbation of gene expression is a key pathogenetic event in PKS. Three genes-ATP6V1G1 in 9q32, GMPS in 3q25.31, and TBX5 in 12q24.21-exhibited concomitant hypermethylation and decreased expression. The i(12p)-positive cells displayed global hypomethylation of gene-poor regions on 12p, a footprint previously associated with constitutional and acquired gains of whole chromosomes as well as with X-chromosome inactivation in females. We hypothesize that this non-genic hypomethylation is associated with chromatin processing that facilitates cellular adaptation to excess genetic material.

lncRNA LOC339524 inhibits the proliferation of bladder cancer cells by targeting the miR‑875‑5p/COPS7A signaling axis

“…The results of the current study demonstrated that miR-875-5p served as an oncogene in BCa. COPS7A belongs to the COP9 signalosome complex (CSN) complex ( 28 ). CSN expression has been shown to control cell cycle progression and to be associated with carcinogenesis ( 29 ).…”

Mutation, methylation, and gene expression profiles in dup(1q)-positive pediatric B-cell precursor acute lymphoblastic leukemia

“…We and others have previously identified altered methylation patterns in cases with genomic gains, such as hypomethylation of gene-poor regions on the trisomic/tetrasomic chromosomes in HeH, on chromosomes 7 and 14 in colon cancer with trisomies of these chromosomes, on chromosome 8 in constitutional trisomy 8 mosaicism, and on 12p in Pallister–Killian syndrome with gain of i(12p)[ 50 – 54 ]. We hence hypothesized that also gain of 1q might be associated with such methylation changes and ascertained the methylation status of cancer tissue-specific differentially methylated regions, promoters, CpG islands, shores, and shelves on 1q.…”

A case of a parthenogenetic 46,XX/46,XY chimera presenting ambiguous genitalia

“…2a). Next, to confirm chimerism, we analyzed the B-allele frequency of autosomes and the X chromosome [13,14]. We found both a region showing five allele combinations, where possible SNP genotypes were BB-BB, BB-BA, BB-AA, BA-AA, and AA-AA, which means that there were three or four chromosome sets, and a region showing three allele combinations, where the possible SNP genotypes were BB-BB, AB-AB, and AA-AA, which means that there were two identical chromosome sets in the autosomes (Fig.…”