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Cell Journal، جلد ۱۳، شماره Supplement، صفحات ۰-۰
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عنوان انگلیسی I-17: Molecular Studies on Cervical Cancer :Expression Profiling, HPV and Genetic Alterations in Cervical Cancers from India
چکیده انگلیسی مقاله According to World Cancer Report, global cancer rates could increase by 50% to 15 million by 2020. The report provides clear evidence that action on smoking, diet and infections can prevent one third of cancers, another third can be cured if detected early. Human papilloma virus (HPV) plays a major role in the etiology of cervical cancer as well as oro-pharyngeal cancers, both of which are major cancers in India. Early detection of the high risk HPV types has been shown to reduce the cervical cancer burden. Cervical cancer patients present at an advanced stage in India. Five year survival of patients from FIGO stage III onwards is less than 45%. Radiotherapy is the treatment of choice although emergence of resistance is an unsolved problem. To identify gene signatures for radiation response and metastasis in cervical cancer, pretreatment samples of FIGO stage IIIB of the disease have been analyzed using DNA microarray with Agilent 4*44K chip. Raw data obtained were normalized, filtered and analyzed using Genespring GX11 software. The samples were grouped with respect to the response to the treatment, as either having no evidence of disease (NED) or with local recurrence (LR) or distant metastasis (DM) after a minimum follow-up of 60 months. A set of genes discriminating the two groups of patients in both analyzing groups were identified. Genes with significantly different (p≤0.05 and fold difference 2) expression between the two groups were selected and a prediction model was established using support vector machine algorithm. This model was then used to predict the prognosis in test set of samples. The respective gene sets could predict about >72% and >85% of test samples correctly in NED vs LR and NED vs DM respectively. Using high throughput HPV genotyping we have studied 24 different HPV types in a cohort of cervical cancer patients. We have also studied the site of integration of the virus using APOT (Amplification of Papilloma virus Oncogene Transcript) assay. Sixty two percent of the samples (175/280) tested positive for HPV by the high throughput Luminex bead array. Out of these 88% (154/175) were HPV16+; 11% (19/175) were HPV 18+. HPV16+ as well as HPV negative patients fared better after therapy; HPV18+ patients had a poor prognosis. Majority (78%) of the cervical cancer samples showed HPV integration. 17% (12/70) had HPV in both integrated and episomal form. Few (22%) had HPV in the episomal form. Patients with episomal form of HPV had a good prognosis. Integration sites were more frequent in 1p and 3q loci. Genetic alterations in the cervical cancer samples are being studied by next generation sequencing technology. Whole exome sequencing has been carried out for a few samples along with their corresponding normal blood samples using Illumina GA2X sequencer. Novel SNVs including SNPs and indels have been identified in important genes. This data will be presented.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/1500
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