Gain of imprinting of SLC22A18 sense and antisense transcripts in human breast cancer

Abstract

The 11p15.5 region harbors three imprinted sense/antisense transcript pairs, SLC22A18/SLC22A18AS, IGF2/IGF2AS (PEG8), and KCNQ1/KCNQ1OT1 (LIT1). SLC22A18 (solute carrier family 22 (organic cation transporter) member 18) and its antisense transcript SLC22A18AS are paternally suppressed in fetal samples. In adult tissue, SLC22A18 displays polymorphic imprinting, but the imprinting status of SLC22A18AS remains elusive. SLC22AI8 DNA-PCR-RFLP analysis using NlaIII restriction digestion identified SLC22A18 heterozygotes within this breast tissue cohort (n = 89). Commercial sequencing identified informative SLC22A18AS samples. Random hexamer-primed cDNA synthesis, SLC22A18/SLC22A18AS-specific PCR, and imprinting evaluation by commercial sequencing demonstrated that SLC22A18AS displays a nonimprinted profile in reduction mastectomies (n = 6). However, SLC22A18 showed a gain of imprinting (GOI) in 1/4 of these normal cases. In the malignant cohort, GOI was also demonstrated in 18% for SLC22A18 and 14% for SLC22A18AS, occurring concomitantly in one case. This study reports the imprinting status of SLC22A18AS in adult tissue, and shows that GOI affects both the sense, and antisense transcripts at this locus in human breast tissue.

The solute carrier (SLC) complement of the human genome: Phylogenetic classification reveals four major families

“…2a. This class constitutes mainly metal ion transporters from nine families (SLC5, 9,11,12,20,24,30,39 and 41 families) but also the sulfate ion transporters from the SLC26 family. In addition, these families include in total 20 orphan transporters, which also are likely to transport some sort of metal ions, which means that the human genome could contain close to 80 transporters for metal ions.…”

Germline and somatic imprinting in the nonhuman primate highlights species differences in oocyte methylation

“…This embryonic stage-specific expression may also be true in primates and could account for the partial imprinting seen in term extraembryonic tissues (Lee et al 1997;Caspary et al 1998;Gould and Pfeifer 1998). Published findings on human SLC22A18 suggest that polymorphic imprinting is evident in adult liver and kidney (Dao et al 1998;Gallagher et al 2006), though the population frequency of this occurrence is unknown. Our analysis of SLC22A18 in macaques in these same tissues showed consistent biallelic expression (Fig.…”

Promoter characterization and regulation of expression of an imprinted gene SLC22A18AS

“…Imprinting studies on this particular sense-antisense pair suggest that both genes are paternally imprinted and maternally expressed (Cooper et al, 1998;Bajaj et al, 2004), although the SLC22A18AS gene shows biallelic expression in adult breast tissue (Gallagher et al, 2006). The human chromosomal region 11p15.5 harbors three imprinted sense-antisense transcript pairs: IGF2/IGF2AS(PEG8), KCNQ1/KCNQ1OT1(LIT1), and SLC22A18/SLC22A18AS (Gallagher et al, 2006).…”