Analysis of FHIT transcripts in cervical and endometrial cancers

Su, Tsung‐Hsien; Wang, Jyh-Chwan; Tseng, H H; Chang, Chih‐Peng; Chang, Ting-Chen; Wei, Hong-Jian; Chang, Jan‐Gowth

doi:10.1002/(sici)1097-0215(19980413)76:2<216::aid-ijc8>3.3.co;2-t

Cited by 9 publications

(11 citation statements)

References 15 publications

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“…The tissues were frozen immediately after surgical resection and stored in liquid nitrogen until extraction of either DNA or RNA. DNA extraction was performed as previously described [21,22]. Clinically, eight cases were stage I, 35 cases were stage II, eight cases were stage III, and two cases were stage IV.…”

Section: Samplesmentioning

confidence: 99%

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Disturbance of circadian gene expression in breast cancer

et al. 2009

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To explore the mechanism of the disruption of circadian rhythm in breast cancer, we examined the expression of nine circadian genes in 53 newly diagnosed breast cancers by immunohistochemical staining, mutational analysis, and methylation analysis of the promoter of circadian genes. Our results showed that 37 of the 53 breast cancer tissues had hypermethylation on the promoters of PER1, PER2, CRY1, or BMAL1. Twenty-five out of 53 paired noncancerous (normal) tissues had methylation on the promoter of PER1 or CRY1. Our results indicated a higher frequency of concurrent methylation of PER1 and CRY1 promoters in cancerous and normal tissues. Promoter methylation of the PER1 correlates with c-erbB2 immunohistochemical reaction of > or = 2+ (p = 0.012) and has a strong inverse correlation with estrogen receptor positivity (p = 0.016). We further analyzed the patterns of circadian gene expression by immunohistochemical methods and found that homogeneous expression of PER2 or BMAL1 is significantly associated with lymph node metastasis and poor prognosis. PER2 heterogeneous expression correlates with <2+ c-erbB2 immunohistochemical reaction. Heterogeneous expression of CLOCK is associated significantly with 3-year survival. In conclusion, the expression pattern of circadian genes might be a biomarker for the prognosis of breast cancer.

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Section: Samplesmentioning

confidence: 99%

“…Genomic DNA was modified with sodium bisulfite and methylation-specific PCRs were performed as described [21][22][23] with some modifications. Two pairs of primers for the promoter of each circadian gene were used to determine the methylation status of the promoter.…”

Section: Methylation-specific Pcr Analysis Of Circadian Genesmentioning

confidence: 99%

Disturbance of circadian gene expression in breast cancer

et al. 2009

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“…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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“…With only one exception all of the aberrant transcripts described here retain the sequences coded by exon 9, and it is perhaps of interest to note that aberrant FHIT transcripts from tumour types including ovarian, endometrial and cervical (Greenspan et al, 1997;Hendricks et al, 1997;Su et al, 1998), digestive tract (Chen et al, 1997), lung (Sozzi et al, 1996a;Fong et al, 1997), pancreatic (Simon et al, 1998), merkel cell carcinoma (Sozzi et al, 1996b), oesophageal (Michael et al, 1997), head and neck (Mao et al, 1996) and breast (Negrini et al, 1996) similarly retain exon 9 sequences in the aberrant transcripts. This may be particularly pertinent in the light of sequences present in this exon with high homology to the Kozaks translation initiation sequence (Kozak, 1984) and a small open reading frame, although as yet no peptide has been documented as arising from this site.…”

Section: Discussionmentioning

confidence: 86%

HIT family genes: FHIT but not PKCI-1/HINT produces altered transcripts in colorectal cancer

et al. 1999

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Summary Forty-five colorectal adenocarcinomas were examined for alterations in the HIT family genes FHIT and PKCI-1/HINT by a combination of reverse transcriptase polymerase chain reaction and DNA sequencing. In all cases a single transcript corresponding to the reported sequence was detected using primers specific for the PKCI-1/HINT gene. In contrast multiple transcripts were detected using primers specific for the FHIT gene transcript. 6% (3/45) of tumours evinced no detectable expression of any FHIT transcript and a further 12% (6/45) produced only the normal full length transcripts. Ninety-six aberrant transcripts were characterized from the remaining tumours. Deviations from the normal full length sequence characterized included deletions, insertions of novel sequences, a point mutation as well as the usage of a putative alternate splice site in exon 10. Message variants were detected with approximately equal frequency in all tumour stages with the exception that templates with insertions were found solely in Dukes' stage B tumours (P < 0.001). With the exception of the putative alternate splice site, aberrant transcripts were not detected in matched normal mucosa. These results suggest that members of the HIT family of genes are only selectively involved in tumorigenesis and that perturbation of FHIT gene expression is an early event in colorectal tumorigenesis.

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Analysis of FHIT transcripts in cervical and endometrial cancers

Cited by 9 publications

References 15 publications

Disturbance of circadian gene expression in breast cancer

Disturbance of circadian gene expression in breast cancer

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

HIT family genes: FHIT but not PKCI-1/HINT produces altered transcripts in colorectal cancer

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