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biokit


biokit
 

Various studies of ovarian cancer sequencing plasticity


By biokit at 2014-12-03 02:36:10
metastatic lesions. This study shows a new way of therapeutic intervention, disease site indicates that the plurality of sampling and sequencing may be effective in targeting therapy necessary. The study, published in the journal Genome Research of November 12.

Ovarian cancer is a malignant ovarian tumor, refers to the growth in the ovarian cancer, wherein 90% to 95% for primary ovarian cancer, another 5% to 10% for the other parts of the primary cancer to metastasis ovary. Due to the lack of ovarian cancer early symptoms, even if symptoms are not specific, the role of screening and limited, so early diagnosis is difficult. Thus, although the incidence of ovarian cancer is lower than cervical and endometrial cancer ranks third in gynecological malignancies, but the mortality rate is more than cervical and endometrial cancer sum, topped the gynecological cancer each year worldwide 220 000 people suffering from this disease, which has 1,400,001 people died, is the biggest threat to women's health, serious illness, which is an urgent need for improved treatment of this disease.

A study published in the journal Genome Research on Nov. 12 by the University Medical Center Utrecht, the Netherlands and the United States Life Technologies Corporation scientists, using a variety of sequencing methods to study the genetic mutations in ovarian cancer. The researchers detected a total of 27 women from the primary tumor and metastasis from ovarian cancer three late ( Rat Kidney injury molecule 1 ELISA Kit http://www.cusabio.com/ELISA_Kit-82149/ ) lesions cancer biopsy samples collected. Researchers by using a variety of methods to analyze the samples of cancer and normal tissue samples match, including transcriptome sequencing, paired-end sequencing and DNA sequencing of several target panel. All from Life Technologies sequencing company Applied Biosystems SOLiD 5500xL and Ion Personal Genome Machine (PGM) carried on using Life of Ion AmpliSeq Comprehensive Cancer Panel, which is a encompasses more than 400 cancer-related genes panel. This study represents the first use include 409 oncogenes this panel of peer-reviewed publications.

Sequencing data indicate that each patient has a tumor in a significant degree of genetic heterogeneity. From coding mutation spectrum, the spectrum of genomic structural variation and genetic expression of the spectrum can be seen, this is obvious. Notably, some individuals exhibit independent drive TP53 mutations (driver mutations), each of them only one sub-sample of the concentrated presence of ovarian cancer. This level of heterogeneity of cancer is also reflected in each instance different evolutionary path, there is a linear development of some cancers, while examples of the performance of the early branch TP53, wherein each branch has its own set of genetic mutations.

"Ovarian cancer is only in a late stage - often large tumor mass, the entire abdominal cavity with a large number of metastases, are typically able to diagnose," the first author of the study, the main research Utrecht University Medical Center who Wigard P. Kloosterman said. "With the major chunk of resection, we get a lot of samples from each of these women, which allows us to study the internal cancer chemotherapy or other medications before the application of heterogeneity. This current studies, represents the most extensive data set, revealed extensive heterogeneity may be one of the possible reasons for this is so difficult to treat a disease. "

Studies have shown that among patients with tumor biopsies from the same presence, there are significant differences in gene expression. This includes the integration of the Hedgehog pathway members WNT-- hormone and tumor biopsy subset - expression variation. Currently, the treatment of ovarian cancer targeting being developed, appropriate patient stratification method is necessary for successful treatment. For example, the use of Hedgehog pathway inhibitors is a new therapeutic strategy proved useful only in those patients showed changes in the Hedgehog signaling. The results of this study indicate that the targeted therapy patient stratification adjustment method will need to analyze each patient multiple biopsies.

"The study of the drug for the individual efforts taken a critical first step, this study describes a spectrum of mutations in human cancer." Co-author of Life Technologies R & P director, is the study of Timothy Harkins said. "This study is complete and fast, because the experimental design not only contains an individual genetic description of all tumors, but also uses a variety of sequencing technology, so that these mutations at the same speed they are detected to verify."

"Tumors from individual differences in the mutation spectrum of women showed sequencing a plurality of samples from a single patient may be before a drug regimen can be designed as required," Life Technologies chief medical officer Paul Billings said. "In this study, we observed that in every women to very different evolutionary paths, which may have been missed, even if only a part of the primary tumor or metastases is only one sequencing data show that, if only one transfer will be by biopsy and sequenced a large number of relevant driver mutations and drug targets may be missed, which would bring bad treatment outcomes."
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