Abnormalities of Fragile Histidine Triad Genomic and Complementary DNAs in Cervical Cancer: Association With Human Papillomavirus Type

Muller, Carolyn Y.; O’Boyle, John D.; Fong, Kwun M.; Wistuba, Ignacio I.; Biesterveld, Eric J.; Ahmadian, Mohsen; Miller, David S.; Gazdar, Adi F.; Minna, John D.

doi:10.1093/jnci/90.6.433

Cited by 45 publications

(31 citation statements)

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“…HPV16 genomes have been found integrated in the vicinity of the FHIT coding sequence and the presence of HPV16 DNA was associated with LOH in the FHIT region (Muller et al, 1998;Butler et al, 2000;Yoshino et al, 2000). Detailed typing of HR HPV in our study did not show any associations between abnormal FHIT transcript expression and presence of specific HR HPV types or all HR HPV taken together.…”

Section: Discussioncontrasting

confidence: 57%

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confidence: 89%

“…Integration of HPV16 sequences at the FHIT locus has been described but this does not appear to be site specific (Wagatsuma et al, 1990;Wilke et al, 1995). HPV16 sequences were not present in abnormal FHIT transcripts (Muller et al, 1998) and the presence of HR HPV E6/E7 transcripts and abnormal FHIT transcripts were negatively correlated in cervical cancer (Segawa et al, 1999).In this investigation, abnormal FHIT gene expression based on the detection of abnormal FHIT transcripts or a reduction of immunohistochemical staining for FHIT protein was studied in 281 and 114 biopsies respectively, of normal cervix and CIN lesions. We assessed whether these indicators of genomic instability at chromosome location 3p14.2 were present at an early stage, when the oncogenic potential of HR HPV is not yet fully expressed.…”

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confidence: 96%

“…Inconsistent results were also obtained in the analysis of abnormal transcripts encoded by the fragile histidine triad (FHIT) gene at chromosome 3p14.2. These are also indicative of genomic instability (Sozzi et al, 1996) but the incidence reported varies from 30 to 80% in cervical cancer and 0 to 40% in normal tissue (Greenspan et al, 1997;Chu et al, 1998;Muller et al, 1998;Su et al, 1998;Yoshino et al, 1998;Nakagawa et al, 1999;Segawa et al, 1999). In only one study, which involved FHIT protein staining in 110 paraffin sections, was a reduction in FHIT gene expression observed to correlate with increasing lesion grade (Birrer et al, 1999).…”

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confidence: 99%

“…In only one study, which involved FHIT protein staining in 110 paraffin sections, was a reduction in FHIT gene expression observed to correlate with increasing lesion grade (Birrer et al, 1999). How genetic alterations in chromosome 3p interact with HR HPV is also not clear (Muller et al, 1998;Butler et al, 2000). Integration of HPV16 sequences at the FHIT locus has been described but this does not appear to be site specific (Wagatsuma et al, 1990;Wilke et al, 1995).…”

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Abnormal FHIT expression profiles in cervical intraepithelial neoplastic (CIN) lesions

Terry

Londesborough

et al. 2002

Br J Cancer

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Abnormal fragile histidine triad transcripts were found in 20 -30% of CIN2/3 lesions and 11% of normal cervical biopsies by RT -PCR. Bi-allelic loss of the fragile histidine triad gene and the loss of fragile histidine triad protein expression detectable by immunochemical staining with a polyclonal fragile histidine triad specific antibody was rare. The genomic changes showed no association with the presence of human papillomavirus types which carry high risk for cervical cancer (high risk human papillomavirus) as assessed by a type-specific multiplex PCR. The presence of abnormal fragile histidine triad transcripts in a subset of CIN2/3 lesions with no high risk human papillomavirus suggests that this could be an independent risk factor associated with an alternative carcinogenic pathway. Cervical cancer is the second most common malignancy in women worldwide. It is generally accepted that the development of cervical cancer from precancers (CIN2/3) involves multistep molecular changes and is therefore a preventable disease if precancers are detected and treated early.The major risk factor for CIN2/3 and cancer is infection with high risk human papillomavirus (HR HPV) types which include HPV16, HPV18, HPV31, HPV33, HPV35, HPV45, HPV51, HPV52, HPV56, HPV58, HPV59 and HPV68. One or more of these virus types have been reported to be present in 90 -95% of CIN2/3 lesions and in nearly all cancers (Lorincz et al, 1992;Bosch et al, 1995; Walboomers et al, 1996). However, infection with HR HPV does not invariably lead to the development of high grade cervical lesions and there is a clear requirement for other cofactors, presumably to advance the oncogenic process initiated by HR HPV (zur Hausen, 1999). The effects of co-factors are difficult to measure objectively because of the dominant effects of HR HPV infection but tobacco smoking has consistently been associated with cervical cancer (Szarewski et al, 1996) and has been found recently to induce genomic instability in head and neck cancers (Schantz et al, 2000). Other potential co-factors include oral contraceptive use and other sexually transmitted diseases.Genomic instability has been found in cervical neoplasia and commonly involves the short arm of chromosome 3. Results reported so far are based on small numbers of samples and show no clear correlation between genomic changes and lesion grades (Butler et al, 2000;Yoshino et al, 2000). Allelic loss and microsatellite instability were found to occur in lesions with or without malignant potential in similar proportion Chu et al, 1998;Yoshino et al, 1998;Butler et al, 2000;Lin et al, 2000). Inconsistent results were also obtained in the analysis of abnormal transcripts encoded by the fragile histidine triad (FHIT) gene at chromosome 3p14.2. These are also indicative of genomic instability (Sozzi et al, 1996) but the incidence reported varies from 30 to 80% in cervical cancer and 0 to 40% in normal tissue (Greenspan et al, 1997;Chu et al, 1998;Muller et al, 1998;Su et al, 1998;Yoshino et al, 1998;Nakagawa et al, 1999;...

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confidence: 89%

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confidence: 96%

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confidence: 99%

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confidence: 99%

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