AIM: To search candidate tumor suppressor genes (TSGs) on chromosome 4q through detecting high loss of heterozygosity (LOH) regions in sporadic colorectal carcinoma in Chinese patients. METHODS: Thirteen fluorescent l...AIM: To search candidate tumor suppressor genes (TSGs) on chromosome 4q through detecting high loss of heterozygosity (LOH) regions in sporadic colorectal carcinoma in Chinese patients. METHODS: Thirteen fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by polymerase chain reaction (PCR). PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological factors were performed by χ2 test. RESULTS: Data were collected on all informative loci. The average LOH frequency on 4q was 28.56%. The D4S2915 locus showed highest LOH frequency (36.17%). Two obvious deletion regions were detected: one between D4S3000 and D4S2915 locus (4q12-21.1), another flanked by D4S407 and D4S2939 locus (4q25-31.1). None case showed complete deletion of 4q, most cases displayed interstitial deletion pattern solely. Furthermore, compared with clinicopathological features, a significant relationship was observed between LOH frequencies on D4S3018locus. In tumors larger than 5 cm in diameter, LOH frequency was significantly higher than tumors that were less than 5 cm (56% vs 13.79%, P = 0.01). On D4S1534 locus, LOH was significantly associated with liver metastasis (80% vs 17.25%, P = 0.012). No relationship was detected on other locus compared with clinicopathologial features. CONCLUSION: By high resolution deletion mapping, two high frequency regions of LOH (4q12-21.1 and 4q25-31.1) were detected, which may contribute to locate TSGs on chromosome 4q involved in carcinogenesis and progression of sporadic colorectal carcinoma.展开更多
AIM To investigate the impact of thymidylate synthase(TYMS), KRAS and BRAF in the survival of metastatic colorectal cancer(m CRC) patients treated with chemotherapy. METHODS Clinical data were collected retrospectivel...AIM To investigate the impact of thymidylate synthase(TYMS), KRAS and BRAF in the survival of metastatic colorectal cancer(m CRC) patients treated with chemotherapy. METHODS Clinical data were collected retrospectively from records of consecutive patients with m CRC treated with fluoropyrimidine-based chemotherapy from 1/2005 to 1/2007. Formalin-fixed paraffin-embedded tissues were retrieved for analysis. TYMS genotypes were identified with restriction fragment analysis PCR, while KRAS and BRAF mutation status was evaluated using real-time PCR assays. TYMS gene polymorphisms of each of the 3' untranslated region(UTR) and 5'UTR were classified into three groups according to the probability they have for high, medium and low TYMS expression(and similar levels of risk) based on evidence from previous studies. Univariate and multivariate survival analyses were performed.RESULTS The analysis recovered 89 patients with m CRC(46.1% de novo metastatic disease and 53.9% relapsed). Of these, 46 patients(51.7%) had colon cancer and 43(48.3%) rectal cancer as primary. All patients were treated with fluoropyrimidine-based chemotherapy(5FU or capecitabine) as single-agent or in combination with irinotecan or/and oxaliplatin or/and bevacizumab. With a median follow-up time of 14.8 mo(range 0-119.8), 85 patients(95.5%) experienced disease progression, and 63 deaths(70.8%) were recorded. The 3-year and 5-year OS rate was 25.4% and 7.7% while the 3-year progression-free survival rate was 7.1%. Multivariate analysis of TYMS polymorphisms, KRAS and BRAF with clinicopathological parameters indicated that TYMS 3'UTR polymorphisms are associated with risk for disease progression and death(P < 0.05 and P < 0.03 respectively). When compared to tumors without any del allele(genotypes ins/ins and ins/loss of heterozygosity(LOH) linked with high TYMS expression) tumors with del/del genotype(low expression group) and tumors with ins/del or del/LOH(intermediate expression group) have lower risk for disease progression(HR = 0.432, 95%CI: 0.198展开更多
Objective: To investigate possible correlations between tumor location and gen etic alterations in a series of oligodendrogliomas.Methods: A series of 158 cons ecutive oligodendrogliomas were retrospectively reviewed....Objective: To investigate possible correlations between tumor location and gen etic alterations in a series of oligodendrogliomas.Methods: A series of 158 cons ecutive oligodendrogliomas were retrospectively reviewed. In each case, the radi ologic picture and the chromosome 1p (chr 1p) status of the tumor detected by th e loss of heterozygosity technique were analyzed. Correlation between tumor loca tion and molecular profile was made by χ2 tests. Results: Eighty-eight of the 158 patients had low-grade oligodendrogliomas, and 70 had anaplastic oligodendr ogliomas. Overall, oligodendrogliomas with chr 1p loss were located preferential ly in the anterior part of the brain, whereas tumors with intact chr 1p affected mainly the posterior part of the brain (p = 0.0038). In terms of lobar involvem ent, a preferential location of oligodendrogliomas with chr 1p loss was found in the frontal lobes as compared with the temporal, parietal, and occipital tumors (p < 0.01). Conclusion:There is a significant correlation between loss of heter ozygosityon chromosome lp and tumor location in oligodendrogliomas,suggesting th at subtypes of oligodendrogliomas could derive from site-specific precursors.展开更多
基金The National Natural Science Foundation of China, No. 30080016 and No. 30470977
文摘AIM: To search candidate tumor suppressor genes (TSGs) on chromosome 4q through detecting high loss of heterozygosity (LOH) regions in sporadic colorectal carcinoma in Chinese patients. METHODS: Thirteen fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by polymerase chain reaction (PCR). PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological factors were performed by χ2 test. RESULTS: Data were collected on all informative loci. The average LOH frequency on 4q was 28.56%. The D4S2915 locus showed highest LOH frequency (36.17%). Two obvious deletion regions were detected: one between D4S3000 and D4S2915 locus (4q12-21.1), another flanked by D4S407 and D4S2939 locus (4q25-31.1). None case showed complete deletion of 4q, most cases displayed interstitial deletion pattern solely. Furthermore, compared with clinicopathological features, a significant relationship was observed between LOH frequencies on D4S3018locus. In tumors larger than 5 cm in diameter, LOH frequency was significantly higher than tumors that were less than 5 cm (56% vs 13.79%, P = 0.01). On D4S1534 locus, LOH was significantly associated with liver metastasis (80% vs 17.25%, P = 0.012). No relationship was detected on other locus compared with clinicopathologial features. CONCLUSION: By high resolution deletion mapping, two high frequency regions of LOH (4q12-21.1 and 4q25-31.1) were detected, which may contribute to locate TSGs on chromosome 4q involved in carcinogenesis and progression of sporadic colorectal carcinoma.
基金Supported by Kapodistrias,National and Kapodistrian University of Athens,No.70/3/8006(Pythagoras II,EPEAEK II,GSRT)and No.70/3/9114Spathis A was supported during data collection by No.70/3/8462[PENED European Social Fund(75%)and the Greek Ministry of Development-GSRT(25%)]
文摘AIM To investigate the impact of thymidylate synthase(TYMS), KRAS and BRAF in the survival of metastatic colorectal cancer(m CRC) patients treated with chemotherapy. METHODS Clinical data were collected retrospectively from records of consecutive patients with m CRC treated with fluoropyrimidine-based chemotherapy from 1/2005 to 1/2007. Formalin-fixed paraffin-embedded tissues were retrieved for analysis. TYMS genotypes were identified with restriction fragment analysis PCR, while KRAS and BRAF mutation status was evaluated using real-time PCR assays. TYMS gene polymorphisms of each of the 3' untranslated region(UTR) and 5'UTR were classified into three groups according to the probability they have for high, medium and low TYMS expression(and similar levels of risk) based on evidence from previous studies. Univariate and multivariate survival analyses were performed.RESULTS The analysis recovered 89 patients with m CRC(46.1% de novo metastatic disease and 53.9% relapsed). Of these, 46 patients(51.7%) had colon cancer and 43(48.3%) rectal cancer as primary. All patients were treated with fluoropyrimidine-based chemotherapy(5FU or capecitabine) as single-agent or in combination with irinotecan or/and oxaliplatin or/and bevacizumab. With a median follow-up time of 14.8 mo(range 0-119.8), 85 patients(95.5%) experienced disease progression, and 63 deaths(70.8%) were recorded. The 3-year and 5-year OS rate was 25.4% and 7.7% while the 3-year progression-free survival rate was 7.1%. Multivariate analysis of TYMS polymorphisms, KRAS and BRAF with clinicopathological parameters indicated that TYMS 3'UTR polymorphisms are associated with risk for disease progression and death(P < 0.05 and P < 0.03 respectively). When compared to tumors without any del allele(genotypes ins/ins and ins/loss of heterozygosity(LOH) linked with high TYMS expression) tumors with del/del genotype(low expression group) and tumors with ins/del or del/LOH(intermediate expression group) have lower risk for disease progression(HR = 0.432, 95%CI: 0.198
文摘Objective: To investigate possible correlations between tumor location and gen etic alterations in a series of oligodendrogliomas.Methods: A series of 158 cons ecutive oligodendrogliomas were retrospectively reviewed. In each case, the radi ologic picture and the chromosome 1p (chr 1p) status of the tumor detected by th e loss of heterozygosity technique were analyzed. Correlation between tumor loca tion and molecular profile was made by χ2 tests. Results: Eighty-eight of the 158 patients had low-grade oligodendrogliomas, and 70 had anaplastic oligodendr ogliomas. Overall, oligodendrogliomas with chr 1p loss were located preferential ly in the anterior part of the brain, whereas tumors with intact chr 1p affected mainly the posterior part of the brain (p = 0.0038). In terms of lobar involvem ent, a preferential location of oligodendrogliomas with chr 1p loss was found in the frontal lobes as compared with the temporal, parietal, and occipital tumors (p < 0.01). Conclusion:There is a significant correlation between loss of heter ozygosityon chromosome lp and tumor location in oligodendrogliomas,suggesting th at subtypes of oligodendrogliomas could derive from site-specific precursors.
