THE ANALYSIS OF THE SLC22A18 GENE AND ITS NATURAL ANTISENSE
TRANSCRIPTS IN HUMAN PAPILLARY THYROID TUMORS
Irena Martin-Kleiner1, Miljenko Radetić2, Ivana Grbeša1, Domagoj Parazajder2, Miljenko
Kovačić2, Martina Radetić2, Koraljka Gall-Trošelj1
of Molecular Medicine, Ruder Bošković Institute, Zagreb
of Zagreb, Sveti Duh General Hospital, Department of Otorynolaringal and
Cervicofacial Surgery, Zagreb
Corresponding author: kleiner@irb.hr
1Division
2University
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 RTPCR–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.
Key words: SLC22A18, thyroid cancer, LOH