Mutation analysis of the THRA1 gene in breast cancer: deletion/fusion of the gene to a novel sequence on 17q in the BT474 cell line

Item Type:	Article
Title:	Mutation analysis of the THRA1 gene in breast cancer: deletion/fusion of the gene to a novel sequence on 17q in the BT474 cell line
Creators Name:	Futreal, P.A. and Cochran, C. and Marks, J.R. and Iglehart, J.D. and Zimmerman, W. and Barrett, J.C. and Wiseman, R.W.
Abstract:	We have previously described a common region of deletion and allele loss on chromosome 17q in sporadic breast cancers that is likely to contain a tumor suppressor gene. The region, mapped to 17q12-q21, was bordered by D17S250 and D17S579 on the centromeric and telomeric sides, respectively. This deletion region overlaps the BRCA1 locus, which predisposes to familial breast and ovarian cancer. The most frequent loss of heterozygosity was observed at the thyroid hormone receptor alpha (THRA1) locus. Southern analysis revealed a rearrangement of THRA1 in the BT474 breast cancer cell line. This rearrangement represented a deletion of exons 8-10 of one THRA1 allele that was also coamplified with ERBB2. Northern blots showed two mutant transcripts in BT474 cells. Analysis of the mutant transcripts revealed fusion of the THRA1 exon 7 by splicing to a novel sequence designated BTR for "BT474 transcribed rearrangement." BTR was found to be highly conserved and mapped to 17q. The deletion in BT474 cells spans the entire BRCA1 region. To search for additional mutations in the THRA1 gene, all nine protein-encoding exons of THRA1 were examined for point mutations via single strand conformation analysis in a series of primary breast tumors, breast cancer cell lines, and lymphoblastoid cell lines derived from the youngest affected members of several German breast cancer families. No point mutations were detected, including the unrearranged THRA1 allele in BT474. We have thus excluded THRA1 as a commonly mutated sporadic breast cancer tumor suppressor gene and as the BRCA1 gene.
Keywords:	Amino Acid Sequence, Base Sequence, Breast Neoplasms, Cell Line, Chromosome Mapping, Conserved Sequence, Cultured Tumor Cells, Human Chromosomes Pair 17, Molecular Cloning, DNA Mutational Analysis, DNA Primers, Exons, Gene Deletion, Gene Rearrangement, Genetic Markers, Genetic Transcription, Messenger RNA, Molecular Sequence Data, Neoplasm DNA, Northern Blotting, Point Mutation, Poly A, Polymerase Chain Reaction, Thyroid Hormone Receptors
Source:	Cancer Research
ISSN:	0008-5472
Publisher:	American Association for Cancer Research
Volume:	54
Number:	7
Page Range:	1791-1794
Date:	1 April 1994
Official Publication:	http://cancerres.aacrjournals.org/content/54/7/1791.abstract
PubMed:	View item in PubMed

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