"Gain of imprinting of SLC22A18 sense and antisense transcripts in human breast cancer".
E Gallagher a, A Mc Goldrick a, WY Chung a, O Mc Cormack a, M Harrison b, M Kerin c, PA Dervan a, b, and A Mc Cann a, @
a School of Medicine and Medical Science, UCD Conway Institute
of Biomolecular and Biomedical Research, Belfield, Dublin 4, Ireland
b Department of Pathology, Mater Misericordiae Hospital,
Eccles Street, Dublin 7, Ireland
c Clinical Science Institute, University College Hospital
Galway, Ireland
@ Corresponding author. Fax: +353 1 7166888.
E-mail: amanda.mccann@ucd.ie
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.
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