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Gallagher, E,Goldrick, AM,Chung, WY,Cormack, OM,Harrison, M,Kerin, M,Dervan, PA,Cann, AM
Gain of imprinting of SLC22A18 sense and antisense transcripts in human breast cancer
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SLC22A18 SLC22A18AS 11p15.5 breast cancer gain of imprinting loss of heterozygosity natural antisense transcript imprinted genes ORGANIC CATION TRANSPORTER CHROMOSOME SEGMENT 11P15.5 GENE IDENTIFICATION MUTATIONS KIDNEY REGION BWR1A
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. SLC22A18 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 mastectornies (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. (c) 2006 Elsevier Inc. All rights reserved.
DOI 10.1016/j.ygeno.2006.02.004
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