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J Chen - One of the best experts on this subject based on the ideXlab platform.
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Patterns of genomic Loss of Heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer
British Journal of Cancer, 2012Co-Authors: V Abkevich, K M Timms, B T Hennessy, J Potter, M S Carey, L A Meyer, K Smith-mccune, R Broaddus, K H Lu, J ChenAbstract:Background: Defects in BRCA1 , BRCA2 , and other members of the homologous recombination pathway have potential therapeutic relevance when used to support agents that introduce or exploit double-stranded DNA breaks. This study examines the association between homologous recombination defects and genomic patterns of Loss of Heterozygosity (LOH). Methods: Ovarian tumours from two independent data sets were characterised for defects in BRCA1 , BRCA2 , and RAD51C , and LOH profiles were generated. Publically available data were downloaded for a third independent data set. The same analyses were performed on 57 cancer cell lines. Results: Loss of Heterozygosity regions of intermediate size were observed more frequently in tumours with defective BRCA1 or BRCA2 ( P =10^−11). The homologous recombination deficiency (HRD) score was defined as the number of these regions observed in a tumour sample. The association between HRD score and BRCA deficiency was validated in two independent ovarian cancer data sets ( P =10^−5 and 10^−29), and identified breast and pancreatic cell lines with BRCA defects. Conclusion: The HRD score appears capable of detecting homologous recombination defects regardless of aetiology or mechanism. This score could facilitate the use of PARP inhibitors and platinum in breast, ovarian, and other cancers.
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Patterns of genomic Loss of Heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer
British journal of cancer, 2012Co-Authors: V Abkevich, B T Hennessy, M S Carey, L A Meyer, K Smith-mccune, R Broaddus, Kirsten Timms, John D. Potter, J ChenAbstract:Patterns of genomic Loss of Heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer
Yusuke Nakamura - One of the best experts on this subject based on the ideXlab platform.
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Loss of Heterozygosity at the cyp2d6 locus in breast cancer implications for germline pharmacogenetic studies
Journal of the National Cancer Institute, 2015Co-Authors: Matthew P Goetz, Yusuke Nakamura, James Sun, Vera J Suman, Grace O Silva, Charles M Perou, Nancy J Cox, Philip J Stephens, Vincent A Miller, Jeffrey S RossAbstract:Background: Controversy exists regarding the impact of CYP2D6 genotype on tamoxifen responsiveness. We examined Loss of Heterozygosity (LOH) at the CYP2D6 locus and determined its impact on genotyping error when tumor tissue is used as a DNA source.
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frequent Loss of Heterozygosity in the region including brca1 on chromosome 17q in squamous cell carcinomas of the esophagus
Cancer Research, 1994Co-Authors: Takahiro Mori, Takahisa Aoki, Toshiki Matsubara, Du Xiqun, Tetsuro Nishihira, Futoshi Iida, Shozo Mori, Yusuke NakamuraAbstract:Ninety-four esophageal squamous cell carcinomas were examined for Loss of Heterozygosity at several loci on the long arm of chromosome 17 (17q), using restriction fragment length polymorphism markers. Loss of Heterozygosity was observed in 56 (62%) of 91 tumors that were informative with at least one marker. Comparison of these results with clinicopathological data indicated that the Losses on chromosome 17q had occurred at an early stage of carcinogenesis. Detailed deletion mapping in these tumors revealed that the region commonly deleted was within the segment between loci defined by two markers at chromosomal band 17q21.3.
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frequent Loss of Heterozygosity for loci on chromosome 8p in hepatocellular carcinoma colorectal cancer and lung cancer
Cancer Research, 1992Co-Authors: Mitsuru Emi, Yoshiyuki Fujiwara, Setsuo Hirohashi, Hitoshi Tsuda, Toshifusa Nakajima, Eiju Tsuchiya, Yoshiharu Maeda, Kouji Tsuruta, Michiko Miyaki, Yusuke NakamuraAbstract:Frequent Loss of Heterozygosity at chromosomal loci in a specific tumor type may indicate the presence of a tumor suppressor gene. We have examined Loss of Heterozygosity on chromosome 8p in paired tumor and constitutional DNA from 346 patients representing seven different types of human cancer. Frequent allelic Losses were observed in hepatocellular carcinoma (22 of 46 cases, 47.8%), in colorectal cancer (12 of 26, 46.2%), and in non-small cell lung cancer (14 of 35, 40.0%), in contrast to low frequencies detected in breast cancer (5 of 56, 8.9%) and renal cell carcinoma (2 of 27, 7.4%). Ovarian cancer and gastric cancer showed intermediate frequencies of 33.3% and 22.2%. Subsequent analysis of 120 hepatocellular carcinomas and 94 colorectal cancers with five polymorphic markers along the short arm of chromosome 8 defined commonly deleted regions within the same chromosomal interval, 8p23. 1-8p21.3, suggesting that one or more tumor suppressor genes for both cancers may be present in that region.
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detection of Loss of Heterozygosity at the human tp53 locus using a dinucleotide repeat polymorphism
Genes Chromosomes and Cancer, 1992Co-Authors: Michael H Jones, Yusuke NakamuraAbstract:Loss of Heterozygosity at the TP53 locus occurs frequently in many types of cancer and requires polymorphic markers for detection. Several polymorphisms at the TP53 locus have been described previously, and polymerase chain reaction (PCR)-based assays have been developed to detect these polymorphisms. However, these polymorphisms have relatively low levels of Heterozygosity and are often uninformative. We report here the detection of Loss of Heterozygosity at the TP53 locus in various human cancers by using a highly informative dinucleotide repeat polymorphism.
V Abkevich - One of the best experts on this subject based on the ideXlab platform.
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Patterns of genomic Loss of Heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer
British Journal of Cancer, 2012Co-Authors: V Abkevich, K M Timms, B T Hennessy, J Potter, M S Carey, L A Meyer, K Smith-mccune, R Broaddus, K H Lu, J ChenAbstract:Background: Defects in BRCA1 , BRCA2 , and other members of the homologous recombination pathway have potential therapeutic relevance when used to support agents that introduce or exploit double-stranded DNA breaks. This study examines the association between homologous recombination defects and genomic patterns of Loss of Heterozygosity (LOH). Methods: Ovarian tumours from two independent data sets were characterised for defects in BRCA1 , BRCA2 , and RAD51C , and LOH profiles were generated. Publically available data were downloaded for a third independent data set. The same analyses were performed on 57 cancer cell lines. Results: Loss of Heterozygosity regions of intermediate size were observed more frequently in tumours with defective BRCA1 or BRCA2 ( P =10^−11). The homologous recombination deficiency (HRD) score was defined as the number of these regions observed in a tumour sample. The association between HRD score and BRCA deficiency was validated in two independent ovarian cancer data sets ( P =10^−5 and 10^−29), and identified breast and pancreatic cell lines with BRCA defects. Conclusion: The HRD score appears capable of detecting homologous recombination defects regardless of aetiology or mechanism. This score could facilitate the use of PARP inhibitors and platinum in breast, ovarian, and other cancers.
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Patterns of genomic Loss of Heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer
British journal of cancer, 2012Co-Authors: V Abkevich, B T Hennessy, M S Carey, L A Meyer, K Smith-mccune, R Broaddus, Kirsten Timms, John D. Potter, J ChenAbstract:Patterns of genomic Loss of Heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer
Cesare Bordi - One of the best experts on this subject based on the ideXlab platform.
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association between recurrence of sporadic colorectal cancer high level of microsatellite instability and Loss of Heterozygosity at chromosome 18q
Diseases of The Colon & Rectum, 2004Co-Authors: Leopoldo Sarli, Lorena Bottarelli, Giovanni Bader, Domenico Iusco, Silvia Pizzi, Renato Costi, Tiziana Dadda, Marco Bertolani, Luigi Roncoroni, Cesare BordiAbstract:PURPOSE: Microsatellite instability and Loss of Heterozygosity of chromosomes 18q, 8p, and 4p are genetic alterations commonly found in colorectal cancer. We investigated whether these genetic markers allow for the stratification of patients with Stage II to III colorectal cancer into groups with different recurrence risks, and with different prognoses. METHODS: Tumors of 113 patients were evaluated for Loss of Heterozygosity of chromosomes 18q, 8p, and 4p and for microsatellite instability by use of six microsatellite markers. Genetic alterations involving each of these genetic markers were examined for association with disease recurrences and survival. RESULTS: Loss of Heterozygosity of chromosomes 18q, informative in 96 percent of cases, in Stage III tumors was associated with higher risk of overall recurrence (P <0.001), local recurrence (P < 0.001), distant metastases (P < 0.001), decreased overall survival (P = 0.002), and disease-free survival (P < 0.001). The recurrence rates and survival rates among patients with Stage II colorectal cancer were independent of Loss of Heterozygosity of chromosome 18q. Stage III and Loss of Heterozygosity of chromosome 8p also were associated with a higher risk of recurrences when these factors were considered individually. In multivariate analysis, only Loss of Heterozygosity of chromosome 18q was independently associated with risk of recurrences (P < 0.001) and with disease-free survival (P = 0.001). No correlation was observed between microsatellite instability and recurrence rates. However, microsatellite instability was associated with improved overall survival (P = 0.04) and with a longer disease-free interval (P = 0.002). Only in five cases (16.7 percent) was it possible to perform resection of recurrences; two of these patients had microsatellite instability tumor. In no cases was it possible to resect recurrence of tumors with Loss of Heterozygosity of chromosome 18q. CONCLUSIONS: Loss of Heterozygosity of chromosome 18q is an informative genetic marker, which in resected Stage III colorectal cancer can be used to predict recurrences and survival. Microsatellite instability identified cases that, even in the case of recurrence, have a more favorable prognosis.
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Association between recurrence of sporadic colorectal cancer, high level of microsatellite instability, and Loss of Heterozygosity at chromosome 18q.
Diseases of the colon and rectum, 2004Co-Authors: Leopoldo Sarli, Lorena Bottarelli, Giovanni Bader, Domenico Iusco, Silvia Pizzi, Renato Costi, Marco Bertolani, Luigi Roncoroni, Tiziana D'adda, Cesare BordiAbstract:PURPOSE: Microsatellite instability and Loss of Heterozygosity of chromosomes 18q, 8p, and 4p are genetic alterations commonly found in colorectal cancer. We investigated whether these genetic markers allow for the stratification of patients with Stage II to III colorectal cancer into groups with different recurrence risks, and with different prognoses. METHODS: Tumors of 113 patients were evaluated for Loss of Heterozygosity of chromosomes 18q, 8p, and 4p and for microsatellite instability by use of six microsatellite markers. Genetic alterations involving each of these genetic markers were examined for association with disease recurrences and survival. RESULTS: Loss of Heterozygosity of chromosomes 18q, informative in 96 percent of cases, in Stage III tumors was associated with higher risk of overall recurrence (P
Songbin Fu - One of the best experts on this subject based on the ideXlab platform.
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Allelotyping for Loss of Heterozygosity on chromosome 18 in gastric cancer.
World Journal of Gastroenterology, 2004Co-Authors: Jingcui Yu, Songbin FuAbstract:AIM: To investigate the association between Loss of Heterozygosity (LOH) on chromosome 18 and sporadic gastric cancer. METHODS: Multiplex PCR was used to screen 14 highly polymorphic microsatellite markers on chromosome 18 in 45 cases of primary gastric cancer. PCR products were separated on polyacrylamide gels and the electrophoresis maps were analyzed with Genescan and Genotyper. RESULTS: The LOH frequencies in gastric cancer at all 14 markers ranged from 10% to 58%. Eleven markers were found with over 20% LOH frequencies, in which 9 markers located in 18q, and 2 markers in 18p. Two overlapping deleted regions were identified: R1 between D18S61-D18S1161 at 18q22 (9cM) with 24% LOH frequency; R2 between D18S462D18S70 at 18q22-23(6cM) with 32% LOH frequency. CONCLUSION: LOH of chromosome 18 (18q and 18p) may be involved in gastric tumorigenesis. Two overlapping deleted fragments suggested that there might be unidentified tumor suppressor genes in those two regions. Yu JC, Sun KL, Liu B, Fu SB. Allelotyping for Loss of Heterozygosity on chromosome 18 in gastric cancer. World J Gastroenterol 2004; 10(13): 1964-1966
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Analysis of Loss of Heterozygosity on 19p in primary gastric cancer
Chinese journal of medical genetics, 2001Co-Authors: Qi Wang, Chen H, Bai J, Baiqiu Wang, Kankan Wang, Zhaoxia Wang, Zhang Q, Wang S, Songbin FuAbstract:OBJECTIVE: To investigate the Loss of Heterozygosity (LOH) frequency of microsatellite loci in primary gastric cancer samples and locate the deleted regions on 19p in which might exist human gastric cancer related genes. METHODS: The LOH of microsatellite loci on chromosome 19p was analyzed using PCR-SSLP-silver stain method in 43 primary gastric cancers and their paired normal tissues. RESULTS: In 43 primary gastric tumors, LOH was detected on the site for D19S424(29.63%), D19S216(11.53%), D19S406 (33.33%), D19S413(8.57%), D19S221(13.15%), D19S226(8.00%), D19S411(6.45%), D19S883(6.89%), and D19S886(10.71%), microsatellite instability (MSI) was found at the same time at locus D19S886 (17.85%). CONCLUSION: The most common LOH occurrence at D19S406 and D19S424 might imply the existence of the potential genes related to the tumorigenesis of gastric cancer in these loci.
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Analysis of Loss of Heterozygosity on 19p in primary gastric cancer
Chinese journal of medical genetics, 2001Co-Authors: Qi Wang, Chen H, Bai J, Baiqiu Wang, Kankan Wang, Zhaoxia Wang, Zhang Q, Wang S, Songbin FuAbstract:OBJECTIVE: To investigate the Loss of Heterozygosity (LOH) frequency of microsatellite loci in primary gastric cancer samples and locate the deleted regions on 19p in which might exist human gastric cancer related genes. METHODS: The LOH of microsatellite loci on chromosome 19p was analyzed using PCR-SSLP-silver stain method in 43 primary gastric cancers and their paired normal tissues. RESULTS: In 43 primary gastric tumors, LOH was detected on the site for D19S424(29.63%), D19S216(11.53%), D19S406 (33.33%), D19S413(8.57%), D19S221(13.15%), D19S226(8.00%), D19S411(6.45%), D19S883(6.89%), and D19S886(10.71%), microsatellite instability (MSI) was found at the same time at locus D19S886 (17.85%). CONCLUSION: The most common LOH occurrence at D19S406 and D19S424 might imply the existence of the potential genes related to the tumorigenesis of gastric cancer in these loci.
