Analysis of the FHIT gene and FRA3B region in sporadic breast cancer, preneoplastic lesions, and familial breast cancer probands

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dc.contributor.authorAhmadian, M
dc.contributor.authorWistuba, II
dc.contributor.authorFong, KM
dc.contributor.authorBehrens, C
dc.contributor.authorKodagoda, DR
dc.contributor.authorSaboorian, MH
dc.contributor.authorShay, J
dc.contributor.authorTomlinson, GE
dc.contributor.authorBlum, J
dc.contributor.authorMinna, JD
dc.contributor.authorGazdar, AF
dc.date.accessioned2025-01-21T01:33:09Z
dc.date.available2025-01-21T01:33:09Z
dc.date.issued1997
dc.description.abstractThe FHIT gene, which spans the FRA3B fragile site at chromosome 3p14.2 is a candidate tumor suppressor gene in breast and other cancers. We investigated FHIT and FRA3B for loss of heterozygosity (LOH); homozygous deletions; abnormal transcripts; and acquired/germ-line point mutations in breast cancer cell lines (n = 32), breast epithelial and stromal cell cultures (n = 18), microdissected invasive (n = 16) and ductal in situ carcinomas (n = 6), and their accompanying normal and abnormal epithelial foci (n = 14). LOH at 3p14.2, especially at FHIT intragenic marker D3S1300, was found in 6 of 16 microdissected invasive tumors and 3 of 6 ductal in situ carcinomas. In accompanying preneoplastic foci, LOH occurred in two of eight intraductal hyperplasias but not in histologically normal ductal epithelium (n = 6). Three of 32 (9%) breast cancer cell lines demonstrated homozygous deletions of FHIT exon 4 (two cases) and exon 5 (one case), which correlated with exon 4-deleted transcripts and loss of the cDNA transcript containing the coding exons 5-9, respectively. Normal mammary cultures and 31 or 32 tumor cell lines (97%) expressed wild-type coding transcripts as well as a minor exon 5-deleted message. Single-strand conformation polymorphism analysis of the coding exons in the 32 tumor and 18 normal breast cell lines and their sequencing revealed four silent polymorphisms and a germ-line histidine triad point mutation (651 G-->T) in a tumor arising in a 70-year-old woman. This mutation was also present in one of her two thus far unaffected daughters. Analysis of additional DNAs from 280 probands of high-risk breast cancer families for other FHIT exon 8 mutations detected an intronic point mutation 13 bases upstream of exon 8. Thus, we have demonstrated relatively early abnormalities of the FHIT/FRA3B region in breast cancer and discovered two rare FHIT germ-line mutations. The expression of a transcript containing the coding exons in nearly all cell lines, including those with germ-line mutations, suggests the possibility that another gene in the FRA3B region may be involved in the pathogenesis of breast cancer.
dc.description.funderNCI NIH HHS
dc.fuente.origenWOS
dc.identifier.eissn1538-7445
dc.identifier.issn0008-5472
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/97379
dc.identifier.wosidWOS:A1997XU39600010
dc.issue.numero17
dc.language.isoen
dc.pagina.final3668
dc.pagina.inicio3664
dc.revistaCancer research
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleAnalysis of the FHIT gene and FRA3B region in sporadic breast cancer, preneoplastic lesions, and familial breast cancer probands
dc.typeartículo
dc.volumen57
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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