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The analysis of the SLC22A18 gene and its natural antisense transcripts in human papillary thyroid tumors

SLC22A18 (solute carrier family 22, organic cation transporter, member18), known as BWR1A, consists of 11 exons spanning a genomic area of 23 kb. This well known member of the cluster of imprinted genes on the chromosome 11 (11p15.5) is paternally imprinted. SLC22A18 codes for a transporter involved in absorption and excretion of neurotransmitters, drugs and xenobiotic. It is predominantly expressed in fetal and adult liver and kidney tissues. LOH and point mutations of the SLC22A18 gene have been found in Wilm's tumor, lung cancer, hepatoblastoma, rhabdomyosarcoma and breast carcinoma cell lines. Abnormalities in the imprinting of SLC22A18 have been found in hepatocellular carcinomas and Wilm’ s tumors. The most frequent abnormality is gain of imprinting (GOI), resulting in a concomitant reduction of expression of SLC22A18. Natural antisense transcripts (NATs) have been implicated in many aspects of eukaryotic gene activity. SLC22A18AS (antisense) is associated to SLC22A18 (sense). These two genes share, in divergent orientations, 31 bp in their 5′ regions (between the first exon of SLC22A18AS and the second exon of SLC22A18). Both LOH and imprinting status of these two genes were analysed by DNA-PCR-RFLP and RT-PCR– RFLP methods, in 40 patients with papillary thyroid cancer. For SLC22A18 16 samples were informative (heterozygotes), while 24 were non-informative. For SLC22A18AS 27 samples were informative, while 11 were non-informative. Partial LOH was detected in 2 of 16 informative SLC22A18, and in 3 of 27 informative SLC22A18AS samples. For SLC22A18, biallelic expression was present in all 16 non-tumorous and corresponding tumorous tissues. Biallelic expression of SLC22A18AS was present in all 27 heterozygous samples, tumorous and non-tumorous. Contrary to adult human liver and breast tissues, in proportion of which SLC22A18 and SLC22A18AS do follow the pattern of genomic imprinting, this phenomen does not seem to be present in adult thyroid tissues.

SLC22A18; thyroid cancer; LOH

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