Abnormalities of fragile histidine triad genomic and complementary DNAs in cervical cancer: association with human papillomavirus type.
J Natl Cancer Inst
; 90(6): 433-9, 1998 Mar 18.
Article
em En
| MEDLINE
| ID: mdl-9521167
ABSTRACT
BACKGROUND:
Chromosome 3p14.2 contains FRA3B, the most active chromosome breakage site in the human genome. The fragile histidine triad (FHIT) gene, a putative tumor suppressor gene, overlaps FRA3B. Human papillomavirus (HPV), a known cofactor in cervical carcinogenesis, can integrate into FRA3B. We examined abnormalities in FHIT and its RNA transcripts in cervical cancer cell lines and tumors. We also investigated the relationship between loss of heterozygosity (LOH) in FHIT/FRA3B and the presence of oncogenic HPV types.METHODS:
Eleven cell lines, 40 tumors (20 fresh and 20 archival), and 10 normal cervical epithelia were examined. Two intragenic polymorphic markers (D3S1300 and D3S4103) and the polymerase chain reaction (PCR) were used to examine FHIT LOH. Reverse transcription-PCR (RT-PCR) analysis and single-strand conformation polymorphism analysis of RT-PCR products were used to characterize FHIT transcripts. Oncogenic HPV types were identified by PCR, using general and type-specific primers.RESULTS:
All normal epithelia, 19 of 20 fresh tumors and nine of 11 cell lines expressed wild-type and, occasionally, exon 8-deleted FHIT transcripts. Additional aberrant FHIT transcripts were seen in nine of 20 fresh tumors and in seven of 11 cell lines. DNA sequencing of the aberrant transcripts revealed a variety of insertions and deletions but no point mutations. Three cell lines also had homozygous FHIT deletions. Oncogenic HPV types (i.e., 16, 18, 31, and 33) were detected in 18 of 20 archival tumors, and, in these tumors, LOH within FHIT was identified in nine of 16 informative cases. HPV 16 was found to be associated with LOH in the FHIT/FRA3B region (P = .041).CONCLUSION:
FHIT/FRA3B is frequently altered in cervical cancer, demonstrating LOH, occasional homozygous deletions, and frequent aberrant transcripts not found in normal epithelia. However, the presence of wild-type transcripts and the lack of protein-altering point mutations raise questions about FHIT's function as a classic tumor suppressor gene in cervical tissue.
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Base de dados:
MEDLINE
Assunto principal:
Infecções Tumorais por Vírus
/
Cromossomos Humanos Par 3
/
DNA de Neoplasias
/
Neoplasias do Colo do Útero
/
Deleção Cromossômica
/
Fragilidade Cromossômica
/
DNA Complementar
/
Infecções por Papillomavirus
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
J Natl Cancer Inst
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos