AberrantFHIT transcripts in squamous cell carcinoma of the uterine cervix

Yoshino, Kiyoshi; Enomoto, Takayuki; Nakamura, Takafumi; Nakashima, Ryo; Wada, Hiroko; Saitoh, Junko; Noda, Kiichiro; Murata, Yuji

doi:10.1002/(sici)1097-0215(19980413)76:2<176::aid-ijc2>3.0.co;2-u

Cited by 33 publications

(21 citation statements)

References 14 publications

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“…This integration occurred between exons 4 and 5 (Zimonjic et al, 1997). The FHIT gene has been specifically studied in cervical carcinomas (Greenspan et al, 1997;Chu et al, 1998;Muller et al, 1998;Yoshino et al, 1998). Aberrant FHIT transcripts were detected in seven out of 11 (63%) CC cell lines and in 35 out of 74 (47%) primary cervical carcinomas of different types and stages (Muller et al, 1998).…”

Section: Loh At 3p and The Fhit Gene In CCmentioning

confidence: 99%

The molecular genetics of cervical carcinoma

1999

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In the pathogenesis of cervical carcinoma there are three major components, two of them related to the role of human papillomaviruses (HPV). First, the effect of viral E6 and E7 proteins. Second, the integration of viral DNA in chromosomal regions associated with well known tumour phenotypes. Some of these viral integrations occur recurrently at specific chromosomal locations, such as 8q24 and 12q15, both harbouring HPV18 and HPV16. And third, there are other recurrent genetic alterations not linked to HPV. Recurrent losses of heterozygosity (LOH) have been detected in chromosome regions 3p14–22, 4p16, 5p15, 6p21–22, 11q23, 17p13.3 without effect on p53, 18q12–22 and 19q13, all of them suggesting the alteration of putative tumour suppressor genes not yet identified. Recurrent amplification has been mapped to 3q+ arm, with the common region in 3q24–28 in 90% of invasive carcinomas. The mutator phenotype, microsatellite instability, plays a minor role and is detected in only 7% of cervical carcinomas. The development of cervical carcinoma requires the sequential occurrence and selection of several genetic alterations. The identification of the specific genes involved, and their correlation with specific tumour properties and stages could improve the understanding and perhaps the management of cervical carcinoma. © 1999 Cancer Research Campaign

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Section: Loh At 3p and The Fhit Gene In CCmentioning

confidence: 99%

The molecular genetics of cervical carcinoma

1999

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“…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.…”

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confidence: 95%

“…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%

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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“…It was previously reported that FHIT expression in 68% of cervical carcinoma cell lines is altered (Hendricks et al 1997). Additional studies have confirmed that the FHIT gene is abnormally expressed in 30-78% of cervical carcinoma cell lines and primary tumors (Yoshino et al 1998). In addition, alteration of FHIT expression occurs early in the development of cervical carcinoma because it can be detected in cervical dysplasia (Connolly et al 2000).…”

Section: Cervical Carcinomamentioning

confidence: 88%