title: Alpha-T-catenin (CTNNA3) displays tumour specific monoallelic expression in urothelial carcinoma of the bladder.
abstract: CTNNA3 (alpha-T-catenin) is imprinted with preferential monoallelic expression of the maternal allele in placental tissue. The allelic expression pattern of CTNNA3 in adult human cancer is unknown and warrants investigation as CTNNA3 stabilizes cellular adherence, a feature which if compromised could enable cells to acquire an increased capability to detach and invade. We document the frequency of monoallelic versus biallelic expression of CTNNA3 in urothelial carcinoma of the bladder (UCB) samples and compare the observed patterns with that found in the paired normal sample. DNA PCR reactions encompassing a transcribable SNP polymorphism within exon 12 of CTNNA3 were sequence analyzed to identify heterozygous cases. A total of 96 samples were analyzed and included 22 paired normal and tumor UCB cases, 38 formalin fixed paraffin embedded (FFPE) UCB samples consisting of 18 noninvasive pTa tumors and 20 lamina propria invasive pT1 tumors and 14 cell lines of various lineages. RT-PCR analysis of 35 heterozygous samples followed by sequence analysis allowed monoallelic versus biallelic patterns to be assigned. We have provided the first demonstration that CTNNA3 displays differing allelic expression patterns in UCB. Specifically, 35% (7/20) of informative UCB, showed monoallelic expression, a feature confined to the tumor, with normal urothelial samples displaying biallelic expression. Real time RT-PCR analyses, demonstrated a significantly lower (P = 0.00039) level of CTNNA3 in the tumor samples compared with the paired normals, all of which displayed biallelic expression. In conclusion, monoallelic and biallelic CTNNA3 expression patterns are demonstrable in tumor bladder tissue, whereas normal cases show only biallelic expression.
authors: School of Medicine and Medical Science (SMMS), UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors: Maria
authors: M
authors: Meehan
authors: Audrey
authors: A
authors: Melvin
authors: Emma
authors: E
authors: Gallagher
authors: James
authors: J
authors: Smith
authors: Alo
authors: A
authors: McGoldrick
authors: Catherine
authors: C
authors: Moss
authors: Steven
authors: S
authors: Goossens
authors: Michèle
authors: M
authors: Harrison
authors: Elaine
authors: E
authors: Kay
authors: John
authors: J
authors: Fitzpatrick
authors: Peter
authors: P
authors: Dervan
authors: Amanda
authors: A
authors: Mc Cann
mesh_terms: D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D018392:Genomic Imprinting; D006579:Heterozygote; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D012306:Risk; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism; D051178:alpha Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C441963:CTNNA3 protein, human; D051178:alpha Catenin