Novel Monoallelically Expressed Candidate Tumor Suppressor Gene for Breast Carcinogenesis on Chromosome 11p15.5

摘要

I have identified a novel Xist-like nuclear transcript (11p-xlnt) which is monoallelically expressed and accumulates in the interphase nucleus at its site of transcription. 11p-xlnt is transcribed from within a narrowly defined 500 kb portion of human chromosome 11p15.5 that exhibits loss of heterozygosity (LOH) in 40% of breast cancers. I have shown that 11p-xlnt is transcribed from within an intron of and antisense to the KvLQT gene and spans at least 40 kb of genomic sequence. Construction and screening of a cDNA library failed to reveal evidence of splicing for this large transcript. While transcription appears to be exclusively from the paternal allele in normal tissues, I have shown that expression occurs from both maternal and paternal alleles in a rhabdomyosarcoma cell line, although expression is found to be monoallelic on a single cell basis by RNA FISH. 11p-xlnt may play a part in local and regional gene regulation at the imprinted domain on chromosome 11p.