Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Clinical Ovarian Cancers Display Extensive Genetic Heterogeneity, Study Suggests Multiple Treatment Protocols May Be Necessary

15.11.2013
Sequencing Study Underscores Difficulty of Treating Ovarian Cancer, Points to Diverse Patterns of Ovarian Cancer Evolution

One of the most comprehensive studies of genetic mutations in ovarian cancer was published today, demonstrating an unprecedented level of genetic variation that exists in both primary tumors and metastatic lesions of ovarian cancer. The study highlights potential new pathways for therapeutic intervention and suggests that sampling and sequencing of multiple disease sites may be required for effective targeted treatments.

The paper, titled “Genomic and transcriptomic plasticity in treatment-naïve ovarian cancer,” is available online at the journal Genome Research and is authored by scientists at the University Medical Center Utrecht in The Netherlands and Life Technologies Corporation in Carlsbad, Calif. With an annual global incidence of 220,000 and mortality of 140,0001, ovarian cancer is a leading cause of cancer deaths in women, making it a disease in urgent need of improved treatment.

The researchers examined a total of 27 archived tumor biopsy samples, both from primary tumors as well as distant metastatic sites, gathered from three women with late stage (IIIC/IV) ovarian cancer. Tumor samples and matched normal tissue samples were analyzed using a variety of methods, including transcriptome and mate-pair sequencing and several targeted gene sequencing panels.

Sequencing was conducted on the Applied Biosystems® SOLiD 5500xL and Ion Personal Genome Machine (PGM™), both from Life Technologies, using Life’s Ion AmpliSeq™ Comprehensive Cancer Panel, a panel of more than 400 genes that have been implicated in cancer. This study represents the first peer-reviewed, scientific publication employing this panel of 409 oncogenes.

The sequencing data revealed a striking degree of genetic heterogeneity within each individual’s cancer. This was evident from profiles of coding mutations, genomic structural variation and gene expression changes. Of note, one of the individuals displayed independent TP53 driver mutations, each of which was present in only subsets of the ovarian tumor samples.

This level of heterogeneity was also manifested in different evolutionary pathways that each instance of cancer took, with some cancers following a linear progression while the TP53 instance displayed early branching, in which each branch has its own genetic set of mutations.

“Ovarian cancers are typically diagnosed when the disease is at an advanced stage and the tumor mass is often large with numerous metastases throughout the abdominal cavity,” said Wigard P. Kloosterman, a principal investigator at the University Medical Center Utrecht and lead author of the study. “Following primary debulking surgery, we obtained a large number of samples from each of these women, which enabled the study of intra-tumor heterogeneity before chemotherapeutic or other drug treatments were applied. The current study, representing the most comprehensive data set to date, reveals extensive heterogeneity, which is probably one of the reasons this disease is so difficult to treat.”

The study did reveal marked gene expression differences between tumor biopsies from the same patient. These include altered expression of WNT, integrin and Hedgehog pathway members in subsets of tumor biopsies. Currently, targeted therapies for ovarian cancer patients are being developed and proper patient stratification is essential for successful treatment. For example, application of Hedgehog pathway inhibitors is an emerging strategy that could only prove useful in those patients displaying changes in Hedgehog signaling. The results from this study suggest that fine-tuning of patient stratification for targeted therapy would require analysis of multiple biopsies per patient.

"This study is a key first step in the community’s effort towards personalized medicine, one in which we characterize the mutational landscape within an individual’s cancer," said Timothy Harkins, a Director of R&D with Life Technologies and co-author on the study. “This study was both comprehensive and rapid, as the experimental design encompassed not only the genetic characterization of all tumors within an individual, but it also used multiple sequencing technologies, allowing mutations to be validated at the same pace that they were detected."

“The divergence of mutation profiles within tumors from individual women suggests that sequencing of multiple samples from a single patient may be necessary before a drug treatment protocol can be devised,” said Paul Billings, Chief Medical Officer for Life Technologies. “Very different evolutionary pathways for each woman were observed in the study, which would have been missed if only one section of the primary tumor or just one of the metastatic lesions had been sequenced. The data suggest that if only one metastasis were to be biopsied and sequenced, a number of relevant driver mutations and druggable targets would likely be missed, which would be expected to lead to poor treatment outcomes."

The Applied Biosystems SOLiD 5500 and Ion Personal Genome Machine (PGM™) are for Research Use Only. Not intended for diagnostic purposes.

1World Cancer Research Fund International http://www.wcrf.org/cancer_statistics/data_specific_cancers/ovarian_cancer_statistics.php
About Life Technologies
Life Technologies Corporation (NASDAQ: LIFE) is a global biotechnology company that is committed to providing the most innovative products and services to leading customers in the fields of scientific research, genetic analysis and applied sciences. With a presence in more than 180 countries, the company's portfolio of 50,000 end-to-end solutions is secured by more than 5,000 patents and licenses that span the entire biological spectrum -- scientific exploration, molecular diagnostics, 21st century forensics, regenerative medicine and agricultural research. Life Technologies has approximately 10,000 employees and had sales of $3.8 billion in 2012.
Life Technologies’ Safe Harbor Statement
This press release includes forward-looking statements about our anticipated results that involve risks and uncertainties. Some of the information contained in this press release, including, but not limited to, statements as to industry trends and Life Technologies’ plans, objectives, expectations and strategy for its business, contains forward-looking statements that are subject to risks and uncertainties that could cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Any statements that are not statements of historical fact are forward-looking statements. When used, the words “believe,” “plan,” “intend,” “anticipate,” “target,” “estimate,” “expect” and the like, and/or future tense or conditional constructions (“will,” “may,” “could,” “should,” etc.), or similar expressions, identify certain of these forward-looking statements. Important factors which could cause actual results to differ materially from those in the forward-looking statements are detailed in filings made by Life Technologies with the Securities and Exchange Commission. Life Technologies undertakes no obligation to update or revise any such forward-looking statements to reflect subsequent events or circumstances.

Life Technologies Contact

Suzanne Clancy
760-602-4545
858-205-4235 (mobile)
Suzanne.Clancy@lifetech.com

Suzanne Clancy | EurekAlert!
Further information:
http://www.lifetech.com

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>